You are here

Weinhold, Kent James

Overview:

In addition to their ongoing HIV/AIDS-related research activities, the Weinhold Laboratory is focused on utilizing a comprehensive repertoire of highly standardized and formerly validated assay platforms to profile the human immune system in order to identify immunologic signatures that predict disease outcomes. These ongoing studies span a broad range of highly relevant clinical arenas, including: 1) cancer (non-small cell lung cancer, head and neck cancer, glioblastoma neoforme, ovarian cancer, and prostate cancer), 2) autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosis, multiple sclerosis, and myasthenia gravis), 3) pulmonary disease (idiopathic pulmonary fibrosis), 4) solid organ transplantation (lung, kidney, liver, and heart), and 5) rare diseases (Pompe disease).


Two of the areas that have been especially active over the past few years include the comprehensive immunologic profiling of cancer patients receiving so-called ‘immune checkpoint blockade’ therapies and the search for immune signatures in lung transplant recipients that track with resistance to CMV infection. The laboratory is conducting immune monitoring studies associated with a Phase I trial of Ipilimumab (anti-CTLA-4) in a neoadjuvant setting for the treatment of non-small cell lung cancer (NSCLC). For this trial we are extensively utilized several polychromatic flow cytometry (PFC) platforms to follow activation, maturation, exhaustion, and proliferation patterns within CD4+ and CD8+ subsets of T-cells. We are also utilizing an intracellular cytokine staining (ICS) platform in efforts to detect anti-tumor associated antigen (TAA) responses by CD4+ and CD8+ T cells from peripheral blood mononuclear cells as well as lymphocytes infiltrating the patients’ tumor. These assays are designed to measure antigen-driven intracellular production of IFN-γ, TNF-α, and IL-2, as well as the degranulation marker CD107. This strategy enables us to not only document individual cytokine responses, but to also assess (through Boolean gating) changes in relative polyfunctionality of the responses. We are performing similar immune monitoring of a Phase II trial evaluating nivolumab (anti-PD-1) alone vs. combined nivolumamb + ipilimumab vs. avastin (bevacizamab) alone in patients with glioblastomas. In both studies, we are seeking to identify pharmacodynamics markers and immune correlates predictive of clinical responses. In recently completed studies in a cohort of lung transplant recipients, we identified specific polyfunctional signatures in CD4+ and CD8+ subsets against CMV pp65 and IE-1 antigens that tracked with resistance to CMV infection (manuscript in preparation). These findings now serve as the basis for a Phase I clinical trial to compare conventional 6-month chemoprophylaxis in lung transplant recipients versus a regimen dictated by the presence or absence of the predictive signatures. This trial is the principal component of a recently awarded Clinical Trials in Organ Transplantation or CTOT award made from the NIH to Duke (Scott Palmer, PI). Ongoing studies will test the hypothesis that these signatures that have been validated in lung transplant recipients will also predict resistance to CMV infection in the context of other solid organ transplants such as kidney, liver, and heart.


Future studies will also attempt to identify predictive signatures for resistance to BK polyomavirus, the cause of graft threatening nephritis in kidney transplant recipients and cystitis in bone marrow transplant recipients. Other human diseases that are presently being subjected to comprehensive immune profiling by the laboratory include idiopathic pulmonary fibrosis (IPF), myasthenia gravis, multiple sclerosis, systemic lupus erythematosus, acute coronary syndrome, and Pompe disease


 


 


Recent publications


Zidar, D.A., Mudd, J.C., Juchnowski, S., Lopes, J.P., Sparks, S., Park, S.S., Ishikawa, M., Osborne, R., Washam, J.B., Chan, C., Funderburg, N.T., Owoyele, A., Alaiti, M.A., Mayuga, M., Orringer, C., Costa, M.A., Simon, D.I., Tatsuoka, C., Califf, R.M., Newby, L.K., Lederman, M.M., and Weinhold, K.J.  Altered maturation status and possible immune exhaustion of CD8 T lymphocytes in the peripheral blood of patients presenting with acute coronary syndromes. Arterioscler., Thromb., and Vasc. Biol. 36(2): 389-397, Feb. 2016 PMID: 26663396


Yi, J.S., Russo, M.A., Weinhold, K.J., and Guptill, J.T. Adaptive immune response to therapy in HMGCR autoantibody myopathy. Muscle Nerve.  53(2): 313-317, Feb. 2016. PMID: 26492512          


Snyder, L.D., Chan, C., Kwon, D., Yi J.S., Martissa, J.A., Copeland, C.A.F., Osborne, R.J., Sparks, S.D., Palmer, S.M., Weinhold, K.J.  Polyfunctional T cell responses predict protection from cytomegalovirus after lung transplant.  Am J Respir Crit Care Med. 193 (1): 78-85, Jan.1, 2016 [PMID 26372850]


Guptill, J.T., Yi, J.S., Sanders, D.B., Guidon, A.C., Juel, V.C., Massey, J.M., Howard, J.F., Jr., Scuderi, F., Bartoccioni, E., Evoli, A. and Weinhold, K.J. “Characterization of B cells in muscle-specific kinase antibody myasthenia gravis. Neurol Neuroimmunol Neuroinflamm. 2015 Feb 26;2(2) e77. [PMID 25745635]


Staats, J.S., Enzor, J.H., Sanchez, A.M., Roundtree, W., Guar, A., Jaimes, M., Denny, T.N., and Weinhold, K.J. “Toward a comprehensive external quality assurance program for polychromatic flow cytometry.” J. Immunol. Methods. 409:44-53, 2014. [PMID 24968072]


Nair, S.K., Tomaras, G.D., Sales A.P., Boczkowski, D., Chan, C., Plonk, K., Dannull, J., Pruitt, S.K., and Weinhold, K.J. “High-throughput identification and dendritic cell-based functional validation of MHC class I-restricted Mycobacterium tuberculosis epitopes.” Scientific Reports. Apr. 23, 2014. [PMID 24755960]


Yi, J.S., Guidon, A., Sparks, S., Osborne, R., Juel, V.C., Massey, J.M., Sanders, D.B., Weinhold, K.J., and Guptill, J.T. “Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis.” Journal of Autoimmunity. 2013 Dec27 doi:1016/j.jaunt2013. 12.005. [PMID: 24378287]

Positions:

Professor of Surgery

Surgery, Surgical Sciences
School of Medicine

Joseph W. and Dorothy W. Beard Professor of Experimental Surgery, in the School of Medicine

Surgery, Surgical Sciences
School of Medicine

Chief, Division of Surgical Sciences

Surgery, Surgical Sciences
School of Medicine

Professor of Immunology

Immunology
School of Medicine

Professor in Pathology

Pathology
School of Medicine

Member of the Duke Human Vaccine Institute

Duke Human Vaccine Institute
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1979

Ph.D. — Thomas Jefferson University

Grants:

EQAPOL - Years 2017 to 2024 - BASE

Administered By
Duke Human Vaccine Institute
AwardedBy
National Institutes of Health
Role
Senior Investigator
Start Date
September 30, 2017
End Date
September 29, 2024

Building Interdisciplinary Research Careers in Women's Health

Administered By
Obstetrics and Gynecology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 26, 2002
End Date
July 31, 2022

Neuro-inflammation in Postoperative Cognitive Dysfunction: CSF and fMRI Studies

Administered By
Anesthesiology, Neuroanesthesia
AwardedBy
National Institutes of Health
Role
Advisor
Start Date
July 15, 2017
End Date
March 31, 2022

Magnetically directed single cell transcriptome analysis in HIV latency

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
August 01, 2014
End Date
August 31, 2021

Immune Profiles to Better Understand Chronic Allograft Dysfunction and Successful Long-term Clinical Outcomes after Human Lung Transplantation

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
AwardedBy
National Institutes of Health
Role
Co-Mentor
Start Date
June 15, 2016
End Date
May 31, 2021

Interdisciplinary Research Training Program in AIDS

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 01, 2010
End Date
August 31, 2020

Bringing PrEP to Campus: Examining Strategies for PrEP Delivery to Historically Black College and Universities (HBCU)

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 2005
End Date
June 30, 2020

Center for AIDS Research

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 2005
End Date
June 30, 2020

Interdisciplinary Training Program in Lung Disease

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
AwardedBy
National Institutes of Health
Role
Preceptor
Start Date
July 01, 2009
End Date
March 31, 2020

Pembroluzimab and Radiation Therapy to Improve Outcome in Localized High-Risk Sarcoma

Administered By
Radiation Oncology
AwardedBy
Association of American Cancer Institutes
Role
Co Investigator
Start Date
May 01, 2017
End Date
February 29, 2020

Lost and Found: The Bone Marrow as Counterproductive Site of T cell Sequestration in GBM

Administered By
Neurosurgery
AwardedBy
Sontag Foundation
Role
Mentor
Start Date
October 01, 2015
End Date
September 30, 2019

Immunological biomarker studies in myasthenia gravis

Administered By
Duke Clinical Research Institute
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 01, 2014
End Date
July 31, 2019

Reversible Immunomodulation as a Strategy for Ischemia Tolerance in Hibernation

Administered By
Anesthesiology, Cardiothoracic
AwardedBy
Foundation for Anesthesia Education and Research
Role
Co-Mentor
Start Date
July 01, 2017
End Date
June 30, 2019

Systemic EGFRvIII-targeted bispecific antibody as immunotherapy for glioblastoma

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
March 01, 2015
End Date
February 28, 2019

Transplant Infectious Diseases Interdisciplinary Research Training Grant

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 01, 2013
End Date
August 31, 2018

Duke KURe Program

Administered By
Obstetrics and Gynecology, Urogynecology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
August 01, 2013
End Date
July 31, 2018

Brain Tumor Targeting Using Tumor-Specific Neuroimmunology

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 15, 2014
End Date
May 31, 2018

VTEU Task D Option 2 Protocol FY.2015.A4D14.0033

Administered By
Duke Human Vaccine Institute
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 2015
End Date
February 28, 2018

VTEU Task D Option 3 Protocol FY.2015.A4D14.0033

Administered By
Duke Human Vaccine Institute
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 2015
End Date
February 28, 2018

VTEU Task D Option 4 Protocol FY.2015.A4D14.0033

Administered By
Duke Human Vaccine Institute
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 2015
End Date
February 28, 2018

LC: HIV Vaccine Trials Network

Administered By
Surgery, Surgical Sciences
AwardedBy
Fred Hutchinson Cancer Research Center
Role
Advisor
Start Date
June 29, 2006
End Date
November 30, 2017

EQAPOL Option 5

Administered By
Duke Human Vaccine Institute
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 30, 2010
End Date
September 29, 2017

EQAPOL - 2016 to 2017 - Option 6 - FLOW

Administered By
Duke Human Vaccine Institute
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
September 30, 2010
End Date
September 29, 2017

Innate immune adaptations of hibernation as a new approach to protection against acute organ injury

Administered By
Anesthesiology, Cardiothoracic
AwardedBy
Society of Cardiovascular Anesthesiologists
Role
Co-Mentor
Start Date
July 01, 2015
End Date
June 30, 2017

High Impact Pilot Project on Myasthenia Gravis and Related Neuromuscular Junction Disorders

Administered By
Neurology, Neuromuscular Disease
AwardedBy
Myasthenia Gravis Foundation
Role
Significant Contributor
Start Date
July 01, 2014
End Date
June 30, 2017

Institutional Training Grant in Pediatric Infectious Disease

Administered By
Pediatrics, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
May 21, 2011
End Date
December 31, 2016

HIV Vaccine Trials Network: LC P5 PF

Administered By
Surgery, Surgical Sciences
AwardedBy
Fred Hutchinson Cancer Research Center
Role
Advisor
Start Date
December 01, 2015
End Date
November 30, 2016

VTEU Task A Protocol FY.2015.A4D14.0033

Administered By
Duke Human Vaccine Institute
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 2015
End Date
August 31, 2016

HIV and Asthma in the Post- ART Era

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
September 13, 2014
End Date
August 31, 2016

Duke 20 patient 'run-up' study of Ipilimumab plus Nivolumab therapy for glioblastoma multiforme

Administered By
Surgery, Surgical Sciences
AwardedBy
Bristol-Myers Squibb Company
Role
Principal Investigator
Start Date
April 16, 2014
End Date
June 30, 2016

Longitudinal assessment of CMV and BK virus immunity in renal transplant patients

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
AwardedBy
National Institutes of Health
Role
Advisor
Start Date
April 15, 2013
End Date
March 31, 2016

HIV Vaccine Trials Network: LC P5 PF

Administered By
Surgery, Surgical Sciences
AwardedBy
Fred Hutchinson Cancer Research Center
Role
Advisor
Start Date
December 01, 2014
End Date
November 30, 2015

LC: HIV Vaccine Trials Network: Phase 1 PF

Administered By
Surgery, Surgical Sciences
AwardedBy
Fred Hutchinson Cancer Research Center
Role
Advisor
Start Date
December 01, 2014
End Date
November 30, 2015

CFAR Minority Supplement:Mentor Meade

Administered By
Duke Global Health Institute
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 15, 2010
End Date
February 28, 2015

ImmunosanT-Nexvax2-1002

Administered By
Surgery, Surgical Sciences
AwardedBy
ImmusanT
Role
Principal Investigator
Start Date
March 05, 2014
End Date
April 30, 2014

Targeting EGFRvIII in Brain Tumors with Bispecific Antibodies

Administered By
School of Medicine
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
May 01, 2013
End Date
April 30, 2014

Novel Cellular Immune Profiles to Predict Lung Disease Outcomes

Administered By
Institutes and Centers
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
May 01, 2011
End Date
August 30, 2013

RNA-based Immunotherapy Targeting Antigens Unique to Brain Tumor Stem Cells

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
August 01, 2008
End Date
May 31, 2013

CTSA UL

Administered By
Institutes and Centers
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 30, 2006
End Date
September 01, 2012

OAR CFAR Director's Meeting

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
May 01, 2011
End Date
June 30, 2012

Neuroimmunology of Vaccines in Adoptive T-cell Therapy for Brain Tumor

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
July 01, 2010
End Date
June 30, 2012

Pre-clinical Translation of Regulatory T-cell Inhibition in Brain Tumors

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
July 01, 2010
End Date
June 30, 2012

International Research Scientist Development Award

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
AwardedBy
National Institutes of Health
Role
Co-Mentor
Start Date
December 01, 2007
End Date
May 31, 2012

Immune profiling of multi-parameter flow cytometry using computational statistics

Administered By
Biostatistics & Bioinformatics
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 24, 2009
End Date
March 31, 2012

Large Scale Antibody and TCell Epitope Discovery

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 2004
End Date
September 29, 2011

Effect on IL-2R Antibody on Regulatory T-cells in Patients with Malignant Gliomas

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Assistant Research Professor
Start Date
January 04, 2008
End Date
December 31, 2009

OAR PSI and CFAR: Prevention/Behavioral Supplement

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 27, 2006
End Date
June 30, 2007

Central Laboratory for the HIV Vaccines Trial Network

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 01, 2000
End Date
September 30, 2006

NCRR FACSAria Cell Sorter

Administered By
Medicine, Duke Human Vaccine Institute
AwardedBy
National Center for Research Resources
Role
Co Investigator
Start Date
April 01, 2004
End Date
March 31, 2006

Host Virus Interactions During Acute Infection

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 1997
End Date
August 31, 2002

Aids Research

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 1989
End Date
May 31, 2002

Viral Control and Immune Reconstitution in HIV Infection

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 1995
End Date
August 31, 2000

Immune Response to Breast Ductal Carcinoma In Situ

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 01, 1992
End Date
August 31, 2000

Anti-Hiv Ctl And Hiv Suppressive Cd8 Cells

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1990
End Date
April 30, 2000

Central Immunology Laboratory For Aids Vaccine Clinical Tr

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 17, 1996
End Date
March 01, 2000

Host Virus Interactions During Acute Infection

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 30, 1996
End Date
August 31, 1999

Viral Control And Immune Reconstitution In Hiv Infection

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 1996
End Date
August 31, 1999

Viral Control & Immune Reconstitution In Hiv Infection

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 30, 1995
End Date
August 31, 1999

Duke University Center For Aids Research

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
July 01, 1994
End Date
June 30, 1999

Anti-Hiv Ctl And Hiv-Suppresive Cd8+ Cells

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
May 01, 1996
End Date
April 30, 1999

Anti-Hiv Ctl And Hiv Suppresive Cd8+ Cells

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
May 01, 1995
End Date
April 30, 1999

Antihiv Ctl And Hiv Suppressive Cd8 Cells

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1990
End Date
April 30, 1999

Spore In Breast Cancer

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 30, 1995
End Date
August 31, 1998

Spore In Breast Cancer

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 30, 1995
End Date
August 31, 1998

Molecularly-Defined Taa As Human Anti-Tumor Ctl Targets

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1993
End Date
July 31, 1997

Molecularly-Defined Taa As Human Anti Tumor Ctl Targets

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1992
End Date
May 31, 1997

Molecularly-Defined Taa As Human Anti-Tumor Ctl Targets

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1992
End Date
May 31, 1997

Molecularly-Defined Taa As Human Anti-Tumor Ctl Targets

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
June 01, 1992
End Date
May 31, 1997

Adoptive Immunotherapy For Aids Lymphoma

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 30, 1993
End Date
August 31, 1996

Pre-Clinical Trials On Prevention & Intervention In Aids

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 29, 1993
End Date
June 30, 1995

Characterization Oa Anti-Hivi Cellular Cytoxicities

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1991
End Date
June 30, 1995

Characterization Of Anti-Hiv 1 Cellular Cytotoxicities

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1990
End Date
June 30, 1995

Characterization Of Anti-Hiv-1 Callular Cytoxicities

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
May 01, 1994
End Date
April 30, 1995

Characterization Of Anti-Hiv1 Cellular Cytoxicities

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
May 01, 1993
End Date
April 30, 1995

Characterization Of Anti-Hiv 1 Cellular Cytoxicities

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1992
End Date
April 30, 1995

Duke University Center For Aids Research

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
July 01, 1993
End Date
June 30, 1994

Developmt Of Anti-Htlv-Iii Specific Agnts & Trmt Apprcs Ti

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
March 01, 1986
End Date
February 01, 1988

Passive Immunotherapy Of Spontaneous Akr Leukemia

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1985
End Date
July 01, 1986
Show More

Publications:

Dendritic cells enhance polyfunctionality of adoptively transferred T cells which target cytomegalovirus in glioblastoma.

Median survival for glioblastoma (GBM) remains <15 months. Human Cytomegalovirus (CMV) antigens have been identified in GBM but not normal brain, providing an unparalleled opportunity to subvert CMV antigens as tumor-specific immunotherapy targets. A recent trial in recurrent GBM patients demonstrated the potential clinical benefit of adoptive T cell therapy (ATCT) of CMV phosphoprotein 65 (pp65)-specific T cells. However, ex vivo analyses from this study found no change in the capacity of CMV pp65-specific T cells to gain multiple effector functions or polyfunctionality, which has been associated with superior antitumor efficacy. Previous studies have shown that dendritic cells (DC) could further enhance tumor-specific CD8+ T-cell polyfunctionality in vivo when administered as a vaccine. Therefore, we hypothesized that vaccination with CMV pp65 RNA-loaded DC would enhance the frequency of polyfunctional CMV pp65-specific CD8+ T cells after ATCT. Here we report prospective results of a pilot trial in which 22 patients with newly-diagnosed GBM were initially enrolled of which 17 patients were randomized to receive CMV pp65-specific T cells with CMV-DC vaccination (CMV-ATCT-DC) or saline (CMV-ATCT-Saline). Patients who received CMV-ATCT-DC vaccination experienced a significant increase in the overall frequencies of IFNγ+, TNFα+, and CCL3+ polyfunctional, CMV-specific CD8+ T cells. These increases in polyfunctional CMV-specific CD8+ T cells correlated with overall survival, although we cannot conclude this was causally related. Our data implicate polyfunctional T-cell responses as a potential biomarker for effective antitumor immunotherapy and support a formal assessment of this combination approach in a larger randomized study.

Authors
Reap, E; Suryadevara, CM; Batich, KA; Sanchez-Perez, L; Archer, GE; Schmittling, RJ; Norberg, PK; Herndon, JE; Healy, P; Congdon, KL; Gedeon, PC; Campbell, OC; Swartz, AM; Riccione, KA; Yi, JS; Hossain-Ibrahim, MK; Saraswathula, A; Nair, SK; Dunn-Pirio, AM; Broome, TM; Weinhold, KJ; Desjardins, A; Vlahovic, G; Mclendon, R; Friedman, AH; Friedman, HS; Bigner, DD; Fecci, PE; Mitchell, DA; Sampson, JH
MLA Citation
Reap, E, Suryadevara, CM, Batich, KA, Sanchez-Perez, L, Archer, GE, Schmittling, RJ, Norberg, PK, Herndon, JE, Healy, P, Congdon, KL, Gedeon, PC, Campbell, OC, Swartz, AM, Riccione, KA, Yi, JS, Hossain-Ibrahim, MK, Saraswathula, A, Nair, SK, Dunn-Pirio, AM, Broome, TM, Weinhold, KJ, Desjardins, A, Vlahovic, G, Mclendon, R, Friedman, AH, Friedman, HS, Bigner, DD, Fecci, PE, Mitchell, DA, and Sampson, JH. "Dendritic cells enhance polyfunctionality of adoptively transferred T cells which target cytomegalovirus in glioblastoma." Cancer research (November 2017).
PMID
29093005
Source
epmc
Published In
Cancer Research
Publish Date
2017
DOI
10.1158/0008-5472.can-17-0469

Immune Activation in Early Stage Non-Small Cell Lung Cancer Patients Receiving Neoadjuvant Chemotherapy Plus Ipilimumab.

To determine the immunologic effects of neoadjuvant chemotherapy plus ipilimumab in early stage non-small cell lung cancer (NSCLC) patients.This is a single-arm chemotherapy plus phased ipilimumab Phase II study of 24 treatment-naïve patients with Stage IB-IIIA NSCLC. Patients received neoadjuvant therapy consisting of 3 cycles of paclitaxel with either cisplatin or carboplatin and ipilimumab included in the last 2 cycles.Chemotherapy alone had little effect on immune parameters in PBMCs. Profound CD28 dependent activation of both CD4 and CD8 cells was observed following ipilimumab. Significant increases in the frequencies of CD4+ cells expressing activation markers ICOS, HLA-DR, CTLA-4, and PD-1 were apparent. Likewise, increased frequencies of CD8+ cells expressing the same activation markers, with the exception of PD-1, were observed. We also examined 7 resected tumors and found higher frequencies of activated TILs than those observed in PBMCs. Surprisingly, we found 4 cases of pre-existing tumor-associated antigens (TAA) responses against survivin, PRAME, or MAGE-A3 present in PBMC at baseline, but neither increased frequencies nor the appearance of newly detectable responses following ipilimumab therapy. Ipilimumab had little effect on the frequencies of circulating Tregs and MDSCs.This study did not meet the primary endpoint of detecting an increase in blood based tumor associated antigen T cell responses after ipilimumab. Collectively, these results highlight the immune activating properties of ipilimumab in early stage NSCLC. The immune profiling data for ipilimumab alone can contribute to the interpretation of immunological data from combined immune checkpoint blockade immunotherapies.

Authors
Yi, JS; Ready, N; Healy, P; Dumbauld, C; Osborne, R; Berry, M; Shoemaker, D; Clarke, J; Crawford, J; Tong, BC; Harpole, D; D'Amico, TA; McSherry, F; Dunphy, F; McCall, SJ; Christensen, JD; Wang, X; Weinhold, KJ
MLA Citation
Yi, JS, Ready, N, Healy, P, Dumbauld, C, Osborne, R, Berry, M, Shoemaker, D, Clarke, J, Crawford, J, Tong, BC, Harpole, D, D'Amico, TA, McSherry, F, Dunphy, F, McCall, SJ, Christensen, JD, Wang, X, and Weinhold, KJ. "Immune Activation in Early Stage Non-Small Cell Lung Cancer Patients Receiving Neoadjuvant Chemotherapy Plus Ipilimumab." Clinical cancer research : an official journal of the American Association for Cancer Research (September 26, 2017).
PMID
28951518
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Publish Date
2017
DOI
10.1158/1078-0432.ccr-17-2005

B10 Cell Frequencies and Suppressive Capacity in Myasthenia Gravis Are Associated with Disease Severity.

Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated disease. The mechanisms for loss of self-tolerance in this disease are not well understood, and recently described regulatory B cell (Breg) subsets have not been thoroughly investigated. B10 cells are a subset of Bregs identified by the production of the immunosuppressive cytokine, interleukin-10 (IL-10). B10 cells are known to strongly inhibit B- and T-cell inflammatory responses in animal models and are implicated in human autoimmunity. In this study, we examined quantitative and qualitative aspects of B10 cells in acetylcholine receptor autoantibody positive MG (AChR-MG) patients and healthy controls. We observed reduced B10 cell frequencies in AChR-MG patients, which inversely correlated with disease severity. Disease severity also affected the function of B10 cells, as B10 cells in the moderate/severe group of MG patients were less effective in suppressing CD4 T-cell proliferation. These results suggest that B10 cell frequencies may be a useful biomarker of disease severity, and therapeutics designed to restore B10 cell frequencies could hold promise as a treatment for this disease through restoration of self-tolerance.

Authors
Yi, JS; Russo, MA; Massey, JM; Juel, V; Hobson-Webb, LD; Gable, K; Raja, SM; Balderson, K; Weinhold, KJ; Guptill, JT
MLA Citation
Yi, JS, Russo, MA, Massey, JM, Juel, V, Hobson-Webb, LD, Gable, K, Raja, SM, Balderson, K, Weinhold, KJ, and Guptill, JT. "B10 Cell Frequencies and Suppressive Capacity in Myasthenia Gravis Are Associated with Disease Severity." Frontiers in neurology 8 (January 2017): 34-.
Website
http://hdl.handle.net/10161/15573
PMID
28239367
Source
epmc
Published In
Frontiers in Neurology
Volume
8
Publish Date
2017
Start Page
34
DOI
10.3389/fneur.2017.00034

Adaptive immune response to therapy in hmgcr autoantibody myopathy.

We evaluated the response to immunosuppression in a case of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)-autoantibody myopathy.T- and B-cell subsets were determined by flow cytometry pre- and posttherapy.Baseline immune profiling demonstrated strikingly elevated T-follicular helper (Tfh) cells and plasmablasts. Immunosuppression resulted in clinical improvement and decreased Tfh cells, plasmablasts, and autoantibodies.Immune profiling in HMGCR-autoantibody myopathy suggests a B-cell-mediated disease. Tfh cells and plasmablasts may be therapeutic biomarkers.

Authors
Yi, JS; Russo, MA; Weinhold, KJ; Guptill, JT
MLA Citation
Yi, JS, Russo, MA, Weinhold, KJ, and Guptill, JT. "Adaptive immune response to therapy in hmgcr autoantibody myopathy." Muscle & nerve 53.2 (February 2016): 313-317.
PMID
26492512
Source
epmc
Published In
Muscle and Nerve
Volume
53
Issue
2
Publish Date
2016
Start Page
313
End Page
317
DOI
10.1002/mus.24947

Altered Maturation Status and Possible Immune Exhaustion of CD8 T Lymphocytes in the Peripheral Blood of Patients Presenting With Acute Coronary Syndromes.

Inflammation in response to oxidized lipoproteins is thought to play a key role in acute coronary syndromes (ACS), but the pattern of immune activation has not been fully characterized. We sought to perform detailed phenotypic and functional analysis of CD8 T lymphocytes from patients presenting with ACS to determine activation patterns and potential immunologic correlates of ACS.We used polychromatic flow cytometry to analyze the cytokine production profiles of naïve, effector, and memory CD8 T cells in patients with ACS compared with control subjects with stable coronary artery disease. ACS was associated with an altered distribution of circulating CD8(+) T-cell maturation subsets with reduced proportions of naïve cells and expansion of effector memory cells. ACS was also accompanied by impaired interleukin-2 production by phenotypically naïve CD8 T cells. These results were validated in a second replication cohort. Naïve CD8 cells from patients with ACS also had increased expression of programmed cell death-1, which correlated with interleukin-2 hypoproduction. In vitro, stimulation of CD8 T cells with oxidized low-density lipoprotein was sufficient to cause programmed cell death-1 upregulation and diminished interleukin-2 production by naïve CD8 T cells.In this exploratory analysis, naïve CD8(+) T cells from patients with ACS show phenotypic and functional characteristics of immune exhaustion: impaired interleukin-2 production and programmed cell death-1 upregulation. Exposure to oxidized low-density lipoprotein recapitulates these features in vitro. These data provide evidence that oxidized low-density lipoprotein could play a role in immune exhaustion, and this immunophenotype may be a biomarker for ACS.

Authors
Zidar, DA; Mudd, JC; Juchnowski, S; Lopes, JP; Sparks, S; Park, SS; Ishikawa, M; Osborne, R; Washam, JB; Chan, C; Funderburg, NT; Owoyele, A; Alaiti, MA; Mayuga, M; Orringer, C; Costa, MA; Simon, DI; Tatsuoka, C; Califf, RM; Newby, LK; Lederman, MM; Weinhold, KJ
MLA Citation
Zidar, DA, Mudd, JC, Juchnowski, S, Lopes, JP, Sparks, S, Park, SS, Ishikawa, M, Osborne, R, Washam, JB, Chan, C, Funderburg, NT, Owoyele, A, Alaiti, MA, Mayuga, M, Orringer, C, Costa, MA, Simon, DI, Tatsuoka, C, Califf, RM, Newby, LK, Lederman, MM, and Weinhold, KJ. "Altered Maturation Status and Possible Immune Exhaustion of CD8 T Lymphocytes in the Peripheral Blood of Patients Presenting With Acute Coronary Syndromes." Arteriosclerosis, thrombosis, and vascular biology 36.2 (February 2016): 389-397.
PMID
26663396
Source
epmc
Published In
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume
36
Issue
2
Publish Date
2016
Start Page
389
End Page
397
DOI
10.1161/atvbaha.115.306112

Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation.

Cytomegalovirus (CMV), which is one of the most common infections after lung transplantation, is associated with chronic lung allograft dysfunction and worse post-transplantation survival. Current approaches for at-risk patients include a fixed duration of antiviral prophylaxis despite the associated cost and side effects.We sought to identify a specific immunologic signature that predicted protection from subsequent CMV.CMV-seropositive lung transplantation recipients were included in the discovery (n = 43) and validation (n = 28) cohorts. Polyfunctional CMV-specific immunity was assessed by stimulating peripheral blood mononuclear cells with CMV pp65 or IE-1 peptide pools and then by measuring T-cell expression of CD107a, IFN-γ, tumor necrosis factor-α (TNF-α), and IL-2. Recipients were prospectively monitored for subsequent viremia. A Cox proportional hazards regression model that considered cytokine responses individually and in combination was used to create a predictive model for protection from CMV reactivation. This model was then applied to the validation cohort.Using the discovery cohort, we identified a specific combination of polyfunctional T-cell subsets to pp65 that predicted protection from subsequent CMV viremia (concordance index 0.88 [SE, 0.087]). The model included both protective (CD107a(-)/IFN-γ(+)/IL-2(+)/TNF-α(+) CD4(+) T cells, CD107a(-)/IFN-γ(+)/IL-2(+)/TNF-α(+) CD8(+) T cells) and detrimental (CD107a(+)/IFN-γ(+)/IL-2(-)/TNF-α(-) CD8(+) T cells) subsets. The model was robust in the validation cohort (concordance index 0.81 [SE, 0.103]).We identified and validated a specific T-cell polyfunctional response to CMV antigen stimulation that provides a clinically useful prediction of subsequent cytomegalovirus risk. This novel diagnostic approach could inform the optimal duration of individual prophylaxis.

Authors
Snyder, LD; Chan, C; Kwon, D; Yi, JS; Martissa, JA; Copeland, CAF; Osborne, RJ; Sparks, SD; Palmer, SM; Weinhold, KJ
MLA Citation
Snyder, LD, Chan, C, Kwon, D, Yi, JS, Martissa, JA, Copeland, CAF, Osborne, RJ, Sparks, SD, Palmer, SM, and Weinhold, KJ. "Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation." American journal of respiratory and critical care medicine 193.1 (January 2016): 78-85.
PMID
26372850
Source
epmc
Published In
American journal of respiratory and critical care medicine
Volume
193
Issue
1
Publish Date
2016
Start Page
78
End Page
85
DOI
10.1164/rccm.201504-0733oc

Characterization of B cells in muscle-specific kinase antibody myasthenia gravis.

To characterize B-cell subsets in patients with muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG).In accordance with Human Immunology Project Consortium guidelines, we performed polychromatic flow cytometry and ELISA assays in peripheral blood samples from 18 patients with MuSK MG and 9 healthy controls. To complement a B-cell phenotype assay that evaluated maturational subsets, we measured B10 cell percentages, plasma B cell-activating factor (BAFF) levels, and MuSK antibody titers. Immunologic variables were compared with healthy controls and clinical outcome measures.As expected, patients treated with rituximab had high percentages of transitional B cells and plasmablasts and thus were excluded from subsequent analysis. The remaining patients with MuSK MG and controls had similar percentages of total B cells and naïve, memory, isotype-switched, plasmablast, and transitional B-cell subsets. However, patients with MuSK MG had higher BAFF levels and lower percentages of B10 cells. In addition, we observed an increase in MuSK antibody levels with more severe disease.We found prominent B-cell pathology in the distinct form of MG with MuSK autoantibodies. Increased BAFF levels have been described in other autoimmune diseases, including acetylcholine receptor antibody-positive MG. This finding suggests a role for BAFF in the survival of B cells in MuSK MG, which has important therapeutic implications. B10 cells, a recently described rare regulatory B-cell subset that potently blocks Th1 and Th17 responses, were reduced, which suggests a potential mechanism for the breakdown in immune tolerance in patients with MuSK MG.

Authors
Guptill, JT; Yi, JS; Sanders, DB; Guidon, AC; Juel, VC; Massey, JM; Howard, JF; Scuderi, F; Bartoccioni, E; Evoli, A; Weinhold, KJ
MLA Citation
Guptill, JT, Yi, JS, Sanders, DB, Guidon, AC, Juel, VC, Massey, JM, Howard, JF, Scuderi, F, Bartoccioni, E, Evoli, A, and Weinhold, KJ. "Characterization of B cells in muscle-specific kinase antibody myasthenia gravis." Neurology(R) neuroimmunology & neuroinflammation 2.2 (April 2015): e77-.
Website
http://hdl.handle.net/10161/10206
PMID
25745635
Source
epmc
Published In
Neurology: Neuroimmunology and Neuroinflammation
Volume
2
Issue
2
Publish Date
2015
Start Page
e77
DOI
10.1212/nxi.0000000000000077

Quantitative proteomics of bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis.

The proteomic analysis of bronchoalveolar lavage fluid (BALF) can give insight into pulmonary disease pathology and response to therapy. Here, we describe the first gel-free quantitative analysis of BALF in idiopathic pulmonary fibrosis (IPF), a chronic and fatal scarring lung disease. We utilized two-dimensional reversed-phase liquid chromatography and ion-mobility-assisted data-independent acquisition (HDMSE) for quantitation of >1000 proteins in immunodepleted BALF from the right middle and lower lobes of normal controls and patients with IPF. Among the analytes that were increased in IPF were well-described mediators of pulmonary fibrosis (osteopontin, MMP7, CXCL7, CCL18), eosinophil- and neutrophil-derived proteins, and proteins associated with fibroblast foci. For additional discovery and targeted validation, BALF was also screened by multiple reaction monitoring (MRM), using the JPT Cytokine SpikeMix library of >400 stable isotope-labeled peptides. A refined MRM assay confirmed the robust expression of osteopontin, and demonstrated, for the first time, upregulation of the pro-fibrotic cytokine, CCL24, in BALF in IPF. These results show the utility of BALF proteomics for the molecular profiling of fibrotic lung diseases and the targeted quantitation of soluble markers of IPF. More generally, this study addresses critical quality control measures that should be widely applicable to BALF profiling in pulmonary disease.

Authors
Foster, MW; Morrison, LD; Todd, JL; Snyder, LD; Thompson, JW; Soderblom, EJ; Plonk, K; Weinhold, KJ; Townsend, R; Minnich, A; Moseley, MA
MLA Citation
Foster, MW, Morrison, LD, Todd, JL, Snyder, LD, Thompson, JW, Soderblom, EJ, Plonk, K, Weinhold, KJ, Townsend, R, Minnich, A, and Moseley, MA. "Quantitative proteomics of bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis." Journal of proteome research 14.2 (February 2015): 1238-1249.
PMID
25541672
Source
epmc
Published In
Journal of Proteome Research
Volume
14
Issue
2
Publish Date
2015
Start Page
1238
End Page
1249
DOI
10.1021/pr501149m

Polyfunctional T Cell Immunity Predicts Cytomegalovirus Infection After Lung Transplant

Authors
Snyder, LD; Chan, C; Kwon, D; Yi, J; Martissa, JA; Copeland, CAF; Osborne, R; Sparks, SD; Palmer, SM; Weinhold, KJ
MLA Citation
Snyder, LD, Chan, C, Kwon, D, Yi, J, Martissa, JA, Copeland, CAF, Osborne, R, Sparks, SD, Palmer, SM, and Weinhold, KJ. "Polyfunctional T Cell Immunity Predicts Cytomegalovirus Infection After Lung Transplant." 2015.
Source
wos-lite
Published In
American journal of respiratory and critical care medicine
Volume
191
Publish Date
2015

COMPARISON OF B10 CELLS IN IMMUNOSLTPPRESSED AND IMMUNOSUPPRESSION NAIVE ACHR plus MG

Authors
Yi, JS; Sanders, DB; Massey, JM; Juel, VC; Weinhold, KJ; Guptill, JT
MLA Citation
Yi, JS, Sanders, DB, Massey, JM, Juel, VC, Weinhold, KJ, and Guptill, JT. "COMPARISON OF B10 CELLS IN IMMUNOSLTPPRESSED AND IMMUNOSUPPRESSION NAIVE ACHR plus MG." October 2014.
Source
wos-lite
Published In
Muscle and Nerve
Volume
50
Issue
4
Publish Date
2014
Start Page
716
End Page
716

Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis.

Muscle specific tyrosine kinase myasthenia gravis (MuSK MG) is a form of autoimmune MG that predominantly affects women and has unique clinical features, including prominent bulbar weakness, muscle atrophy, and excellent response to therapeutic plasma exchange. Patients with MuSK MG have predominantly IgG4 autoantibodies directed against MuSK on the postsynaptic muscle membrane. Lymphocyte functionality has not been reported in this condition. The goal of this study was to characterize T cell responses in patients with MuSK MG. Intracellular production of IFN-gamma, TNF-alpha, IL-2, IL-17, and IL-21 by CD4+ and CD8+ T cells was measured by polychromatic flow cytometry in peripheral blood samples from 11 Musk MG patients and 10 healthy controls. Only one MuSK MG patient was not receiving immunosuppressive therapy. Regulatory T cells (Treg) were also included in our analysis to determine if changes in T cell function were due to altered Treg frequencies. CD8+ T cells from MuSK MG patients had higher frequencies of polyfunctional responses than controls, and CD4+ T cells had higher IL-2, TNF-alpha, and IL-17. MuSK MG patients had a higher percentage of CD4+ T cells producing combinations of IFN-gamma/IL-2/TNF-gamma, TNF-alpha/IL-2, and IFN-gamma/TNF-alpha. Interestingly, Treg numbers and CD39 expression were not different from control values. MuSK MG patients had increased frequencies of Th1 and Th17 cytokines and were primed for polyfunctional proinflammatory responses that cannot be explained by a defect in CD39 expression or Treg number.

Authors
Yi, JS; Guidon, A; Sparks, S; Osborne, R; Juel, VC; Massey, JM; Sanders, DB; Weinhold, KJ; Guptill, JT
MLA Citation
Yi, JS, Guidon, A, Sparks, S, Osborne, R, Juel, VC, Massey, JM, Sanders, DB, Weinhold, KJ, and Guptill, JT. "Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis." J Autoimmun 52 (August 2014): 130-138.
Website
http://hdl.handle.net/10161/10224
PMID
24378287
Source
pubmed
Published In
Journal of Autoimmunity
Volume
52
Publish Date
2014
Start Page
130
End Page
138
DOI
10.1016/j.jaut.2013.12.005

Setting objective thresholds for rare event detection in flow cytometry.

The accurate identification of rare antigen-specific cytokine positive cells from peripheral blood mononuclear cells (PBMC) after antigenic stimulation in an intracellular staining (ICS) flow cytometry assay is challenging, as cytokine positive events may be fairly diffusely distributed and lack an obvious separation from the negative population. Traditionally, the approach by flow operators has been to manually set a positivity threshold to partition events into cytokine-positive and cytokine-negative. This approach suffers from subjectivity and inconsistency across different flow operators. The use of statistical clustering methods does not remove the need to find an objective threshold between between positive and negative events since consistent identification of rare event subsets is highly challenging for automated algorithms, especially when there is distributional overlap between the positive and negative events ("smear"). We present a new approach, based on the Fβ measure, that is similar to manual thresholding in providing a hard cutoff, but has the advantage of being determined objectively. The performance of this algorithm is compared with results obtained by expert visual gating. Several ICS data sets from the External Quality Assurance Program Oversight Laboratory (EQAPOL) proficiency program were used to make the comparisons. We first show that visually determined thresholds are difficult to reproduce and pose a problem when comparing results across operators or laboratories, as well as problems that occur with the use of commonly employed clustering algorithms. In contrast, a single parameterization for the Fβ method performs consistently across different centers, samples, and instruments because it optimizes the precision/recall tradeoff by using both negative and positive controls.

Authors
Richards, AJ; Staats, J; Enzor, J; McKinnon, K; Frelinger, J; Denny, TN; Weinhold, KJ; Chan, C
MLA Citation
Richards, AJ, Staats, J, Enzor, J, McKinnon, K, Frelinger, J, Denny, TN, Weinhold, KJ, and Chan, C. "Setting objective thresholds for rare event detection in flow cytometry." Journal of immunological methods 409 (July 2014): 54-61.
Website
http://hdl.handle.net/10161/14686
PMID
24727143
Source
epmc
Published In
Journal of Immunological Methods
Volume
409
Publish Date
2014
Start Page
54
End Page
61
DOI
10.1016/j.jim.2014.04.002

Toward development of a comprehensive external quality assurance program for polyfunctional intracellular cytokine staining assays.

The External Quality Assurance Program Oversight Laboratory (EQAPOL) Flow Cytometry Program assesses the proficiency of NIH/NIAID/DAIDS-supported and potentially other interested research laboratories in performing Intracellular Cytokine Staining (ICS) assays. The goal of the EQAPOL Flow Cytometry External Quality Assurance Program (EQAP) is to provide proficiency testing and remediation for participating sites. The program is not punitive; rather, EQAPOL aims to help sites identify areas for improvement. EQAPOL utilizes a highly standardized ICS assay to minimize variability and readily identify those sites experiencing technical difficulties with their assays. Here, we report the results of External Proficiency 3 (EP3) where participating sites performed a 7-color ICS assay. On average, sites perform well in the Flow Cytometry EQAP (median score is "Good"). The most common technical issues identified by the program involve protocol adherence and data analysis; these areas have been the focus of site remediation. The EQAPOL Flow Cytometry team is now in the process of expanding the program to 8-color ICS assays. Evaluating polyfunctional ICS responses would align the program with assays currently being performed in support of HIV immune monitoring assays.

Authors
Staats, JS; Enzor, JH; Sanchez, AM; Rountree, W; Chan, C; Jaimes, M; Chan, RC-F; Gaur, A; Denny, TN; Weinhold, KJ
MLA Citation
Staats, JS, Enzor, JH, Sanchez, AM, Rountree, W, Chan, C, Jaimes, M, Chan, RC-F, Gaur, A, Denny, TN, and Weinhold, KJ. "Toward development of a comprehensive external quality assurance program for polyfunctional intracellular cytokine staining assays." Journal of immunological methods 409 (July 2014): 44-53.
Website
http://hdl.handle.net/10161/14674
PMID
24968072
Source
epmc
Published In
Journal of Immunological Methods
Volume
409
Publish Date
2014
Start Page
44
End Page
53
DOI
10.1016/j.jim.2014.05.021

Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells.

Despite aggressive conventional therapy, glioblastoma (GBM) remains uniformly lethal. Immunotherapy, in which the immune system is harnessed to specifically attack malignant cells, offers a treatment option with less toxicity. The expression of cytomegalovirus (CMV) antigens in GBM presents a unique opportunity to target these viral proteins for tumor immunotherapy. Although the presence of CMV within malignant gliomas has been confirmed by several laboratories, its relevance as an immunologic target in GBM has yet to be established. The objective of this study was to explore whether T cells stimulated by CMV pp65 RNA-transfected dendritic cells (DC) target and eliminate autologous GBM tumor cells in an antigen-specific manner.T cells from patients with GBM were stimulated with autologous DCs pulsed with CMV pp65 RNA, and the function of the effector CMV pp65-specific T cells was measured.In this study, we demonstrate the ability to elicit CMV pp65-specific immune responses in vitro using RNA-pulsed autologous DCs generated from patients with newly diagnosed GBM. Importantly, CMV pp65-specific T cells lyse autologous, primary GBM tumor cells in an antigen-specific manner. Moreover, T cells expanded in vitro using DCs pulsed with total tumor RNA demonstrated a 10- to 20-fold expansion of CMV pp65-specific T cells as assessed by tetramer analysis and recognition and killing of CMV pp65-expressing target cells.These data collectively demonstrate that CMV-specific T cells can effectively target glioblastoma tumor cells for immunologic killing and support the rationale for the development of CMV-directed immunotherapy in patients with GBM.

Authors
Nair, SK; De Leon, G; Boczkowski, D; Schmittling, R; Xie, W; Staats, J; Liu, R; Johnson, LA; Weinhold, K; Archer, GE; Sampson, JH; Mitchell, DA
MLA Citation
Nair, SK, De Leon, G, Boczkowski, D, Schmittling, R, Xie, W, Staats, J, Liu, R, Johnson, LA, Weinhold, K, Archer, GE, Sampson, JH, and Mitchell, DA. "Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells." Clinical cancer research : an official journal of the American Association for Cancer Research 20.10 (May 2014): 2684-2694.
PMID
24658154
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
20
Issue
10
Publish Date
2014
Start Page
2684
End Page
2694
DOI
10.1158/1078-0432.ccr-13-3268

High-throughput identification and dendritic cell-based functional validation of MHC class I-restricted Mycobacterium tuberculosis epitopes.

Emergence of drug-resistant strains of the pathogen Mycobacterium tuberculosis (Mtb) and the ineffectiveness of BCG in curtailing Mtb infection makes vaccine development for tuberculosis an important objective. Identifying immunogenic CD8+ T cell peptide epitopes is necessary for peptide-based vaccine strategies. We present a three-tiered strategy for identifying and validating immunogenic peptides: first, identify peptides that form stable complexes with class I MHC molecules; second, determine whether cytotoxic T lymphocytes (CTLs) raised against the whole protein antigen recognize and lyse target cells pulsed with peptides that passed step 1; third, determine whether peptides that passed step 2, when administered in vivo as a vaccine in HLA-A2 transgenic mice, elicit CTLs that lyse target cells expressing the whole protein antigen. Our innovative approach uses dendritic cells transfected with Mtb antigen-encoding mRNA to drive antigen expression. Using this strategy, we have identified five novel peptide epitopes from the Mtb proteins Apa, Mtb8.4 and Mtb19.

Authors
Nair, SK; Tomaras, GD; Sales, AP; Boczkowski, D; Chan, C; Plonk, K; Cai, Y; Dannull, J; Kepler, TB; Pruitt, SK; Weinhold, KJ
MLA Citation
Nair, SK, Tomaras, GD, Sales, AP, Boczkowski, D, Chan, C, Plonk, K, Cai, Y, Dannull, J, Kepler, TB, Pruitt, SK, and Weinhold, KJ. "High-throughput identification and dendritic cell-based functional validation of MHC class I-restricted Mycobacterium tuberculosis epitopes." Scientific Reports 4 (April 23, 2014): 4632-.
PMID
24755960
Source
epmc
Published In
Scientific Reports
Volume
4
Publish Date
2014
Start Page
4632
DOI
10.1038/srep04632

Impact of Concurrent Chemoradiation on T Cell Populations in Patients With Advanced- Stage Oropharyngeal Squamous Cell Carcinoma

Authors
Lee, WT; Medinas, R; Lee, JH; Sparks, S; Brizel, DM; Esclamado, RM; Ready, N; Weinhold, KJ
MLA Citation
Lee, WT, Medinas, R, Lee, JH, Sparks, S, Brizel, DM, Esclamado, RM, Ready, N, and Weinhold, KJ. "Impact of Concurrent Chemoradiation on T Cell Populations in Patients With Advanced- Stage Oropharyngeal Squamous Cell Carcinoma." February 1, 2014.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
88
Issue
2
Publish Date
2014
Start Page
504
End Page
504

Managing Multi-center Flow Cytometry Data for Immune Monitoring.

With the recent results of promising cancer vaccines and immunotherapy1-5, immune monitoring has become increasingly relevant for measuring treatment-induced effects on T cells, and an essential tool for shedding light on the mechanisms responsible for a successful treatment. Flow cytometry is the canonical multi-parameter assay for the fine characterization of single cells in solution, and is ubiquitously used in pre-clinical tumor immunology and in cancer immunotherapy trials. Current state-of-the-art polychromatic flow cytometry involves multi-step, multi-reagent assays followed by sample acquisition on sophisticated instruments capable of capturing up to 20 parameters per cell at a rate of tens of thousands of cells per second. Given the complexity of flow cytometry assays, reproducibility is a major concern, especially for multi-center studies. A promising approach for improving reproducibility is the use of automated analysis borrowing from statistics, machine learning and information visualization21-23, as these methods directly address the subjectivity, operator-dependence, labor-intensive and low fidelity of manual analysis. However, it is quite time-consuming to investigate and test new automated analysis techniques on large data sets without some centralized information management system. For large-scale automated analysis to be practical, the presence of consistent and high-quality data linked to the raw FCS files is indispensable. In particular, the use of machine-readable standard vocabularies to characterize channel metadata is essential when constructing analytic pipelines to avoid errors in processing, analysis and interpretation of results. For automation, this high-quality metadata needs to be programmatically accessible, implying the need for a consistent Application Programming Interface (API). In this manuscript, we propose that upfront time spent normalizing flow cytometry data to conform to carefully designed data models enables automated analysis, potentially saving time in the long run. The ReFlow informatics framework was developed to address these data management challenges.

Authors
White, S; Laske, K; Welters, MJ; Bidmon, N; van der Burg, SH; Britten, CM; Enzor, J; Staats, J; Weinhold, KJ; Gouttefangeas, C; Chan, C
MLA Citation
White, S, Laske, K, Welters, MJ, Bidmon, N, van der Burg, SH, Britten, CM, Enzor, J, Staats, J, Weinhold, KJ, Gouttefangeas, C, and Chan, C. "Managing Multi-center Flow Cytometry Data for Immune Monitoring." Cancer informatics 13.Suppl 7 (January 2014): 111-122.
PMID
26085786
Source
epmc
Published In
Cancer Informatics
Volume
13
Issue
Suppl 7
Publish Date
2014
Start Page
111
End Page
122
DOI
10.4137/cin.s16346

Prolonged B-cell depletion in MuSK myasthenia gravis following rituximab treatment.

Authors
Yi, JS; Decroos, EC; Sanders, DB; Weinhold, KJ; Guptill, JT
MLA Citation
Yi, JS, Decroos, EC, Sanders, DB, Weinhold, KJ, and Guptill, JT. "Prolonged B-cell depletion in MuSK myasthenia gravis following rituximab treatment." Muscle Nerve 48.6 (December 2013): 992-993. (Letter)
Website
http://hdl.handle.net/10161/10207
PMID
24006142
Source
pubmed
Published In
Muscle and Nerve
Volume
48
Issue
6
Publish Date
2013
Start Page
992
End Page
993
DOI
10.1002/mus.24063

PROLONGED B CELL DEPLETION IN MUSK MYASTHENIA GRAVIS FOLLOWING RITUXIMAB TREATMENT

Authors
Yi, JS; Choi, E; Sanders, DB; Weinhold, KJ; Guptill, JT
MLA Citation
Yi, JS, Choi, E, Sanders, DB, Weinhold, KJ, and Guptill, JT. "PROLONGED B CELL DEPLETION IN MUSK MYASTHENIA GRAVIS FOLLOWING RITUXIMAB TREATMENT." October 2013.
Source
wos-lite
Published In
Muscle and Nerve
Volume
48
Issue
4
Publish Date
2013
Start Page
691
End Page
691

HIV-1 gp41 envelope IgA is frequently elicited after transmission but has an initial short response half-life.

Prevention of HIV-1 transmission at mucosal surfaces will likely require durable pre-existing mucosal anti-HIV-1 antibodies (Abs). Defining the ontogeny, specificities and potentially protective nature of the initial mucosal virus-specific B-cell response will be critical for understanding how to induce protective Ab responses by vaccination. Genital fluids from patients within the earliest stages of acute HIV-1 infection (Fiebig I-VI) were examined for multiple anti-HIV specificities. Gp41 (but not gp120) Env immunoglobulin (Ig)A Abs were frequently elicited in both plasma and mucosal fluids within the first weeks of transmission. However, shortly after induction, these initial mucosal gp41 Env IgA Abs rapidly declined with a t(½) of ∼2.7 days. B-cell-activating factor belonging to the TNF family (BAFF) was elevated immediately preceding the appearance of gp41 Abs, likely contributing to an initial T-independent Ab response. HIV-1 transmission frequently elicits mucosal HIV-1 envelope-specific IgA responses targeted to gp41 that have a short half-life.

Authors
Yates, NL; Stacey, AR; Nolen, TL; Vandergrift, NA; Moody, MA; Montefiori, DC; Weinhold, KJ; Blattner, WA; Borrow, P; Shattock, R; Cohen, MS; Haynes, BF; Tomaras, GD
MLA Citation
Yates, NL, Stacey, AR, Nolen, TL, Vandergrift, NA, Moody, MA, Montefiori, DC, Weinhold, KJ, Blattner, WA, Borrow, P, Shattock, R, Cohen, MS, Haynes, BF, and Tomaras, GD. "HIV-1 gp41 envelope IgA is frequently elicited after transmission but has an initial short response half-life." Mucosal Immunol 6.4 (July 2013): 692-703.
PMID
23299618
Source
pubmed
Published In
Mucosal immunology
Volume
6
Issue
4
Publish Date
2013
Start Page
692
End Page
703
DOI
10.1038/mi.2012.107

Plasma cytokine analysis in patients with advanced extremity melanoma undergoing isolated limb infusion.

BACKGROUND: Preprocedure clinical and pathologic factors have failed to consistently differentiate complete response (CR) from progressive disease (PD) in patients after isolated limb infusion (ILI) with melphalan for unresectable in-transit extremity melanoma. METHODS: Multiplex immunobead assay technology (Milliplex MAP Human Cytokine/Chemokine Magnetic Bead Panel, Millipore Corp., Billerica, MA; and Magpix analytical test instrument, Luminex Corp., Austin, TX) was performed on pre-ILI plasma to determine concentrations of selected cytokines (MIP-1α, IL-1Rα, IP-10, IL-1β, IL-1α, MCP-1, IL-6, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β) on a subset of patients (n = 180) who experienced CR (n = 23) or PD (n = 24) after ILI. Plasma from normal donors (n = 12) was also evaluated. RESULTS: Of 180 ILIs performed, 28 % (95 % confidence interval 22-35, n = 50) experienced a CR, 14 % (n = 25) experienced a partial response, 11 % (n = 21) had stable disease, 34 % (n = 61) had PD, and 13 % (n = 23) were not evaluable for response. Tumor characteristics and pharmacokinetics appeared similar between CR (n = 23) and PD (n = 24) patients who underwent cytokine analysis. Although there were no differences in cytokine levels between CR and PD patients, there were differences between the melanoma patients and controls. MIP-1α, IL-1Rα, IL-1β, IL-1α, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β were significantly higher in normal controls compared to melanoma patients, while IP-10 was lower (p < 0.001) in controls compared to melanoma patients. CONCLUSIONS: Patients with unresectable in-transit melanoma appear to have markedly decreased levels of immune activating cytokines compared to normal healthy controls. This further supports a potential role for immune-targeted therapies and immune monitoring in patients with regionally advanced melanoma.

Authors
Shetty, G; Beasley, GM; Sparks, S; Barfield, M; Masoud, M; Mosca, PJ; Pruitt, SK; Salama, AKS; Chan, C; Tyler, DS; Weinhold, KJ
MLA Citation
Shetty, G, Beasley, GM, Sparks, S, Barfield, M, Masoud, M, Mosca, PJ, Pruitt, SK, Salama, AKS, Chan, C, Tyler, DS, and Weinhold, KJ. "Plasma cytokine analysis in patients with advanced extremity melanoma undergoing isolated limb infusion." Ann Surg Oncol 20.4 (April 2013): 1128-1135.
PMID
23456379
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
20
Issue
4
Publish Date
2013
Start Page
1128
End Page
1135
DOI
10.1245/s10434-012-2785-5

Upregulation of IL-1β, IL-6, and CCL-2 by a novel mouse model of pancreatic ischemia-reperfusion injury

BACKGROUND: Little is known about the immunologic events surrounding pancreatic ischemia-reperfusion injury (IRI) because of a lack of established experimental models. The purpose of this study was to develop a mouse model for pancreatic IRI to serve as a basis for the immunologic characterization of pancreatic organ damage at transplantation. METHODS: Reversible ischemia was surgically induced by vascular isolation of the distal pancreas for 0, 10, 20, or 30 min. Mice receiving laparotomy without clamping served as sham-operated controls. After reperfusion, mice were serially assayed for biochemical and histologic evidence of inflammation, proinflammatory cytokine and chemokine production, and inflammatory gene upregulation. RESULTS: After induction of pancreatic IRI, serum amylase and lactate dehydrogenase peaked at 6 hr and returned to baseline by 120 hr after injury in all groups. Mice undergoing 30 min of IRI demonstrated the greatest biochemical evidence of inflammation. Histologic scoring similarly demonstrated marked inflammation in mice subjected to 30-min IRI compared with controls. Serum cytokine/chemokine analysis demonstrated significant upregulation of granulocyte colony-stimulating factor, interferon γ, tumor necrosis factor α, interleukin (IL)-2, IL-1β, IL-6, chemokine (C-C motif) ligand-2, chemokine (C-C motif) ligand-5, chemokine (C-X-C motif) ligand-1, and macrophage inflammatory protein 2. A similar upregulation of ccl2, il1b, il6, fos, hspa1a, hspd1, and cd14 gene expression was detected by real-time polymerase chain reaction analysis of pancreatic tissue. CONCLUSIONS: This novel model of distal pancreatic IRI in the mouse demonstrates time-limited pancreatic inflammation and injury by histologic and biochemical indices. Inflammation may be, in part, a result of the immunologic effects of IL-1β, IL-6, and CCL-2. This model provides a method by which immunologic mechanisms of pancreatic IRI can be elucidated. Copyright © 2013 by Lippincott Williams & Wilkins.

Authors
Lunsford, KE; Baird, BJ; Sempowski, GD; Cardona, DM; Li, Z; Weinhold, KJ; Sudan, DL; Brennan, TV
MLA Citation
Lunsford, KE, Baird, BJ, Sempowski, GD, Cardona, DM, Li, Z, Weinhold, KJ, Sudan, DL, and Brennan, TV. "Upregulation of IL-1β, IL-6, and CCL-2 by a novel mouse model of pancreatic ischemia-reperfusion injury." Transplantation 95.8 (2013): 1000-1007.
Source
scival
Published In
Transplantation
Volume
95
Issue
8
Publish Date
2013
Start Page
1000
End Page
1007
DOI
10.1097/TP.0b013e318286483a

Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform.

Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (P<0.02; log-rank Mantel-Cox test). There was no correlation of protective MHC contributing to infection control. The RM without detectable circulating SIV, now hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform.

Authors
Gabitzsch, ES; Balint-Junior, JP; Xu, Y; Balcaitis, S; Sanders-Beer, B; Karl, J; Weinhold, KJ; Paessler, S; Jones, FR
MLA Citation
Gabitzsch, ES, Balint-Junior, JP, Xu, Y, Balcaitis, S, Sanders-Beer, B, Karl, J, Weinhold, KJ, Paessler, S, and Jones, FR. "Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform." Vaccine 30.50 (November 26, 2012): 7265-7270.
PMID
23041546
Source
pubmed
Published In
Vaccine
Volume
30
Issue
50
Publish Date
2012
Start Page
7265
End Page
7270
DOI
10.1016/j.vaccine.2012.09.058

Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication.

CD8-mediated virus inhibition can be detected in HIV-1-positive subjects who naturally control virus replication. Characterizing the inhibitory function of CD8(+) T cells during acute HIV-1 infection (AHI) can elucidate the nature of the CD8(+) responses that can be rapidly elicited and that contribute to virus control. We examined the timing and HIV-1 antigen specificity of antiviral CD8(+) T cells during AHI. Autologous and heterologous CD8(+) T cell antiviral functions were assessed longitudinally during AHI in five donors from the CHAVI 001 cohort using a CD8(+) T cell-mediated virus inhibition assay (CD8 VIA) and transmitted/founder (T/F) viruses. Potent CD8(+) antiviral responses against heterologous T/F viruses appeared during AHI at the first time point sampled in each of the 5 donors (Fiebig stages 1/2 to 5). Inhibition of an autologous T/F virus was durable to 48 weeks; however, inhibition of heterologous responses declined concurrent with the resolution of viremia. HIV-1 viruses from 6 months postinfection were more resistant to CD8(+)-mediated virus inhibition than cognate T/F viruses, demonstrating that the virus escapes early from CD8(+) T cell-mediated inhibition of virus replication. CD8(+) T cell antigen-specific subsets mediated inhibition of T/F virus replication via soluble components, and these soluble responses were stimulated by peptide pools that include epitopes that were shown to drive HIV-1 escape during AHI. These data provide insights into the mechanisms of CD8-mediated virus inhibition and suggest that functional analyses will be important for determining whether similar antigen-specific virus inhibition can be induced by T cell-directed vaccine strategies.

Authors
Freel, SA; Picking, RA; Ferrari, G; Ding, H; Ochsenbauer, C; Kappes, JC; Kirchherr, JL; Soderberg, KA; Weinhold, KJ; Cunningham, CK; Denny, TN; Crump, JA; Cohen, MS; McMichael, AJ; Haynes, BF; Tomaras, GD
MLA Citation
Freel, SA, Picking, RA, Ferrari, G, Ding, H, Ochsenbauer, C, Kappes, JC, Kirchherr, JL, Soderberg, KA, Weinhold, KJ, Cunningham, CK, Denny, TN, Crump, JA, Cohen, MS, McMichael, AJ, Haynes, BF, and Tomaras, GD. "Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication." J Virol 86.12 (June 2012): 6835-6846.
Website
http://hdl.handle.net/10161/13786
PMID
22514337
Source
pubmed
Published In
Journal of virology
Volume
86
Issue
12
Publish Date
2012
Start Page
6835
End Page
6846
DOI
10.1128/JVI.00437-12

Novel Murine Model of Pancreatic Ischemia Reperfusion Injury Up-Regulates Interleukin-1 Beta, Interleukin-6, and CCL-2

Authors
Lunsford, KE; Jackson-Baird, B; Sempowski, GD; Cardona, DM; Weinhold, KJ; Brennan, TV
MLA Citation
Lunsford, KE, Jackson-Baird, B, Sempowski, GD, Cardona, DM, Weinhold, KJ, and Brennan, TV. "Novel Murine Model of Pancreatic Ischemia Reperfusion Injury Up-Regulates Interleukin-1 Beta, Interleukin-6, and CCL-2." May 2012.
Source
wos-lite
Published In
American Journal of Transplantation
Volume
12
Publish Date
2012
Start Page
220
End Page
220

OMIP-006: phenotypic subset analysis of human T regulatory cells via polychromatic flow cytometry.

This panel was optimized for the enumeration and phenotypic characterization of T regulatory cells (Tregs) within the CD4⁺ T-cell pool using human peripheral blood mononuclear cells (PBMC) using intranuclear and intracellular staining methods. The panel was optimized for HIV⁺ clinical trial specimens through the use of HIV-infected and normal donor PBMC. Because the panel is to be used in the context of testing cryopreserved PBMC obtained from multiple sites participating in clinical trials, it was essential to develop an assay that performed well using cryopreserved PBMC. Other tissue types have not been tested.

Authors
Murdoch, DM; Staats, JS; Weinhold, KJ
MLA Citation
Murdoch, DM, Staats, JS, and Weinhold, KJ. "OMIP-006: phenotypic subset analysis of human T regulatory cells via polychromatic flow cytometry." Cytometry A 81.4 (April 2012): 281-283.
PMID
22319016
Source
pubmed
Published In
Cytometry
Volume
81
Issue
4
Publish Date
2012
Start Page
281
End Page
283
DOI
10.1002/cyto.a.22024

Ontogeny of CD8+T Cells in Acute HIV-1 that Inhibit Autologous and Heterologous Transmitted/Founder (T/F) Viruses

Authors
Freel, SA; Picking, RA; Ferrari, G; Ochsenbauer, C; Kappes, JC; Kirchherr, J; Weinhold, KJ; Soderberg, K; McMichael, AJ; Haynes, BF; Tomaras, GD
MLA Citation
Freel, SA, Picking, RA, Ferrari, G, Ochsenbauer, C, Kappes, JC, Kirchherr, J, Weinhold, KJ, Soderberg, K, McMichael, AJ, Haynes, BF, and Tomaras, GD. "Ontogeny of CD8+T Cells in Acute HIV-1 that Inhibit Autologous and Heterologous Transmitted/Founder (T/F) Viruses." October 2011.
Source
wos-lite
Published In
AIDS Research and Human Retroviruses
Volume
27
Issue
10
Publish Date
2011
Start Page
A13
End Page
A13

High-throughput quantitative analysis of HIV-1 and SIV-specific ADCC-mediating antibody responses.

We have developed a high-throughput platform to detect the presence of HIV-1 and SIV-specific ADCC-mediating antibody responses. The assay is based on the hydrolysis of a cell-permeable fluorogenic peptide substrate containing a sequence recognized by the serine protease, Granzyme B (GzB). GzB is delivered into target cells by cytotoxic effector cells as a result of antigen (Ag)-specific Ab-Fcγ receptor interactions. Within the target cells, effector cell-derived GzB hydrolyzes the substrate, generating a fluorescent signal that allows individual target cells that have received a lethal hit to be identified by flow cytometry. Results are reported as the percentage of target cells with GzB activity (%GzB). Freshly isolated or cryopreserved PBMC and/or NK cells can be used as effector cells. CEM.NKR cells expressing the CCR5 co-receptor are used as a target cells following: (i) coating with recombinant envelope glycoprotein, (ii) infection with infectious molecular clones expressing the Env antigens of primary and lab adapted viruses, or (iii) chronic infection with a variant of HIV-1/IIIB, termed A1953. In addition, primary CD4(+) T cells infected with HIV-1 in vitro can also be used as targets. The assay is highly reproducible with a coefficient of variation of less than 25%. Target and effector cell populations, in the absence of serum/plasma, were used to calculate background (8.6 ± 2.3%). We determined that an initial dilution of 1:50 and 1:100 is required for testing of human and non-human primate samples, respectively. This assay allows for rapid quantification of HIV-1 or SIV-specific ADCC-mediating antibodies that develop in response to vaccination, or in the natural course of infection, thus providing researchers with a new methodology for investigating the role of ADCC-mediating antibodies as correlates of control or prevention of HIV-1 and SIV infection.

Authors
Pollara, J; Hart, L; Brewer, F; Pickeral, J; Packard, BZ; Hoxie, JA; Komoriya, A; Ochsenbauer, C; Kappes, JC; Roederer, M; Huang, Y; Weinhold, KJ; Tomaras, GD; Haynes, BF; Montefiori, DC; Ferrari, G
MLA Citation
Pollara, J, Hart, L, Brewer, F, Pickeral, J, Packard, BZ, Hoxie, JA, Komoriya, A, Ochsenbauer, C, Kappes, JC, Roederer, M, Huang, Y, Weinhold, KJ, Tomaras, GD, Haynes, BF, Montefiori, DC, and Ferrari, G. "High-throughput quantitative analysis of HIV-1 and SIV-specific ADCC-mediating antibody responses." Cytometry A 79.8 (August 2011): 603-612.
PMID
21735545
Source
pubmed
Published In
Cytometry
Volume
79
Issue
8
Publish Date
2011
Start Page
603
End Page
612
DOI
10.1002/cyto.a.21084

Polyfunctional cytomegalovirus-specific immunity in lung transplant recipients receiving valganciclovir prophylaxis.

Cytomegalovirus (CMV) is a common opportunistic infection after lung transplant. Despite effective antiviral medications to treat CMV, invasive CMV disease contributes to lung allograft dysfunction and worse survival. Efforts to prevent CMV have led to the use of valganciclovir prophylaxis for increasingly longer periods after transplant. A pivotal concern with long-term antiviral prophylaxis is that it may prevent or delay the development of CMV-specific immunity and increase the subsequent risk of late onset disease. To address this issue, we conducted a pilot study to determine if CMV-specific immunity was detectable in lung transplant recipients at risk for CMV while on antiviral prophylaxis. Utilizing polychromatic flow cytometry panels, CMV-specific immunity was determined by peripheral blood CD4 and CD8 T cell expression of cytokines in response to the HLA restricted CMV peptides pp65 and IE-1. We determined CMV seropositive lung transplant recipients on valganciclovir for a median of 6 months from transplant have a detectable polyfunctional CMV-specific T cell response which is comparable to seropositive recipients not on antiviral medications and to healthy seropositive nontransplant controls. Thus, valganciclovir prophylaxis does not appear to impair the development of CMV-specific immunity in lung transplantation.

Authors
Snyder, LD; Medinas, R; Chan, C; Sparks, S; Davis, WA; Palmer, SM; Weinhold, KJ
MLA Citation
Snyder, LD, Medinas, R, Chan, C, Sparks, S, Davis, WA, Palmer, SM, and Weinhold, KJ. "Polyfunctional cytomegalovirus-specific immunity in lung transplant recipients receiving valganciclovir prophylaxis." Am J Transplant 11.3 (March 2011): 553-560.
PMID
21219584
Source
pubmed
Published In
American Journal of Transplantation
Volume
11
Issue
3
Publish Date
2011
Start Page
553
End Page
560
DOI
10.1111/j.1600-6143.2010.03405.x

Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection.

In the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therapy-naïve subjects were studied in detail between 1 and 87 weeks following onset of symptoms of acute HIV-1 infection. Synthetic peptides representing the autologous transmitted/founder HIV-1 sequences were used in multiparameter flow cytometry assays to determine the functionality of HIV-1-specific CD8+ T memory cells. In all seven patients, the earliest T cell responses were predominantly oligofunctional, although the relative contribution of multifunctional cell responses increased significantly with time from infection. Interestingly, only the magnitude of the total and not of the poly-functional T-cell responses was significantly associated with the selection of escape mutants. However, the high contribution of MIP-1β-producing CD8+ T-cells to the total response suggests that mechanisms not limited to cytotoxicity could be exerting immune pressure during acute infection. Lastly, we show that epitope entropy, reflecting the capacity of the epitope to tolerate mutational change and defined as the diversity of epitope sequences at the population level, was also correlated with rate of emergence of escape mutants.

Authors
Ferrari, G; Korber, B; Goonetilleke, N; Liu, MKP; Turnbull, EL; Salazar-Gonzalez, JF; Hawkins, N; Self, S; Watson, S; Betts, MR; Gay, C; McGhee, K; Pellegrino, P; Williams, I; Tomaras, GD; Haynes, BF; Gray, CM; Borrow, P; Roederer, M; McMichael, AJ; Weinhold, KJ
MLA Citation
Ferrari, G, Korber, B, Goonetilleke, N, Liu, MKP, Turnbull, EL, Salazar-Gonzalez, JF, Hawkins, N, Self, S, Watson, S, Betts, MR, Gay, C, McGhee, K, Pellegrino, P, Williams, I, Tomaras, GD, Haynes, BF, Gray, CM, Borrow, P, Roederer, M, McMichael, AJ, and Weinhold, KJ. "Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection. (Published online)" PLoS Pathog 7.2 (February 10, 2011): e1001273-.
PMID
21347345
Source
pubmed
Published In
PLoS pathogens
Volume
7
Issue
2
Publish Date
2011
Start Page
e1001273
DOI
10.1371/journal.ppat.1001273

Optimization of a highly standardized carboxyfluorescein succinimidyl ester flow cytometry panel and gating strategy design using discriminative information measure evaluation.

The design of a panel to identify target cell subsets in flow cytometry can be difficult when specific markers unique to each cell subset do not exist, and a combination of parameters must be used to identify target cells of interest and exclude irrelevant events. Thus, the ability to objectively measure the contribution of a parameter or group of parameters toward target cell identification independent of any gating strategy could be very helpful for both panel design and gating strategy design. In this article, we propose a discriminative information measure evaluation (DIME) based on statistical mixture modeling; DIME is a numerical measure of the contribution of different parameters towards discriminating a target cell subset from all the others derived from the fitted posterior distribution of a Gaussian mixture model. Informally, DIME measures the "usefulness" of each parameter for identifying a target cell subset. We show how DIME provides an objective basis for inclusion or exclusion of specific parameters in a panel, and how ranked sets of such parameters can be used to optimize gating strategies. An illustrative example of the application of DIME to streamline the gating strategy for a highly standardized carboxyfluorescein succinimidyl ester (CFSE) assay is described.

Authors
Chan, C; Lin, L; Frelinger, J; Hérbert, V; Gagnon, D; Landry, C; Sékaly, R-P; Enzor, J; Staats, J; Weinhold, KJ; Jaimes, M; West, M
MLA Citation
Chan, C, Lin, L, Frelinger, J, Hérbert, V, Gagnon, D, Landry, C, Sékaly, R-P, Enzor, J, Staats, J, Weinhold, KJ, Jaimes, M, and West, M. "Optimization of a highly standardized carboxyfluorescein succinimidyl ester flow cytometry panel and gating strategy design using discriminative information measure evaluation." Cytometry A 77.12 (December 2010): 1126-1136.
PMID
21053294
Source
pubmed
Published In
Cytometry
Volume
77
Issue
12
Publish Date
2010
Start Page
1126
End Page
1136
DOI
10.1002/cyto.a.20987

Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity.

BACKGROUND: A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA). METHODS: Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study, and selected using criteria specifying that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Adaptive immune responses in16 vaccine recipients and two placebo recipients after the 2nd immunization were evaluated using neutralization assays of sera, as well as ELISpot and ICS assays of cryopreserved PBMCs to assess CD4 and CD8 T-cell responses. In addition, (51)Cr release assays were performed on fresh PBMCs following 14-day stimulation with individual vaccine peptide antigens. RESULTS: 24 subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site-2 after dose 1, and 2 after dose 2. Two other subjects experienced severe systemic reactions consisting of headache, chills, nausea, and myalgia. Both reactions occurred after the second 4 mg dose. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific neutralizing (NT) activity, and 2/7 HLA-B7+ vaccinees had classical CD8 CTL activity detected. However, using both ELISpot and ICS, 8/16 vaccinees (5/7 HLA-B7+) and 0/2 controls had detectable vaccine-specific CD8 T-cell responses. Subjects with moderate or severe systemic or local reactions tended to have more frequent T cell responses and higher antibody responses than those with mild or no reactions. CONCLUSIONS: The severity of local responses related to the formulation of these four peptides in IFA is clinically unacceptable for continued development. Both HIV-specific antibody and T cell responses were induced and the magnitude of response correlated with the severity of local and systemic reactions. If potent adjuvants are necessary for subunit vaccines to induce broad and durable immune responses, careful, incremental clinical evaluation is warranted to minimize the risk of adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT00000886.

Authors
Graham, BS; McElrath, MJ; Keefer, MC; Rybczyk, K; Berger, D; Weinhold, KJ; Ottinger, J; Ferarri, G; Montefiori, DC; Stablein, D; Smith, C; Ginsberg, R; Eldridge, J; Duerr, A; Fast, P; Haynes, BF; AIDS Vaccine Evaluation Group,
MLA Citation
Graham, BS, McElrath, MJ, Keefer, MC, Rybczyk, K, Berger, D, Weinhold, KJ, Ottinger, J, Ferarri, G, Montefiori, DC, Stablein, D, Smith, C, Ginsberg, R, Eldridge, J, Duerr, A, Fast, P, Haynes, BF, and AIDS Vaccine Evaluation Group, . "Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity. (Published online)" PLoS One 5.8 (August 10, 2010): e11995-.
Website
http://hdl.handle.net/10161/4559
PMID
20706632
Source
pubmed
Published In
PloS one
Volume
5
Issue
8
Publish Date
2010
Start Page
e11995
DOI
10.1371/journal.pone.0011995

Phenotypic and functional profile of HIV-inhibitory CD8 T cells elicited by natural infection and heterologous prime/boost vaccination.

Control of HIV-1 replication following nonsterilizing HIV-1 vaccination could be achieved by vaccine-elicited CD8(+) T-cell-mediated antiviral activity. To date, neither the functional nor the phenotypic profiles of CD8(+) T cells capable of this activity are clearly understood; consequently, little is known regarding the ability of vaccine strategies to elicit them. We used multiparameter flow cytometry and viable cell sorts from phenotypically defined CD8(+) T-cell subsets in combination with a highly standardized virus inhibition assay to evaluate CD8(+) T-cell-mediated inhibition of viral replication. Here we show that vaccination against HIV-1 Env and Gag-Pol by DNA priming followed by recombinant adenovirus type 5 (rAd5) boosting elicited CD8(+) T-cell-mediated antiviral activity against several viruses with either lab-adapted or transmitted virus envelopes. As it did for chronically infected virus controllers, this activity correlated with HIV-1-specific CD107a or macrophage inflammatory protein 1beta (MIP-1beta) expression from HIV-1-specific T cells. Moreover, for vaccinees or virus controllers, purified memory CD8(+) T cells from a wide range of differentiation stages were capable of significantly inhibiting virus replication. Our data define attributes of an antiviral CD8(+) T-cell response that may be optimized in the search for an efficacious HIV-1 vaccine.

Authors
Freel, SA; Lamoreaux, L; Chattopadhyay, PK; Saunders, K; Zarkowsky, D; Overman, RG; Ochsenbauer, C; Edmonds, TG; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Haynes, BF; Koup, RA; Graham, BS; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Lamoreaux, L, Chattopadhyay, PK, Saunders, K, Zarkowsky, D, Overman, RG, Ochsenbauer, C, Edmonds, TG, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Haynes, BF, Koup, RA, Graham, BS, Roederer, M, and Tomaras, GD. "Phenotypic and functional profile of HIV-inhibitory CD8 T cells elicited by natural infection and heterologous prime/boost vaccination." Journal of virology 84.10 (May 2010): 4998-5006.
PMID
20200250
Source
epmc
Published In
Journal of virology
Volume
84
Issue
10
Publish Date
2010
Start Page
4998
End Page
5006
DOI
10.1128/jvi.00138-10

A model for harmonizing flow cytometry in clinical trials

Authors
Maecker, HT; McCoy, JP; Amos, M; Elliott, J; Gaigalas, A; Wang, L; Aranda, R; Banchereau, J; Boshoff, C; Braun, J; Korin, Y; Reed, E; Cho, J; Hafler, D; Davis, M; Fathman, CG; Robinson, W; Denny, T; Weinhold, K; Desai, B; Diamond, B; Gregersen, P; Dimeglio, P; Nestle, F; Peakman, M; Villnova, F; Ferbas, J; Field, E; Kantor, A; Kawabata, T; Komocsar, W; Lotze, M; Nepom, J; Ochs, H; O'Lone, R; Phippard, D; Plevy, S; Rich, S; Roederer, M; Rotrosen, D; Yeh, J-H
MLA Citation
Maecker, HT, McCoy, JP, Amos, M, Elliott, J, Gaigalas, A, Wang, L, Aranda, R, Banchereau, J, Boshoff, C, Braun, J, Korin, Y, Reed, E, Cho, J, Hafler, D, Davis, M, Fathman, CG, Robinson, W, Denny, T, Weinhold, K, Desai, B, Diamond, B, Gregersen, P, Dimeglio, P, Nestle, F, Peakman, M, Villnova, F, Ferbas, J, Field, E, Kantor, A, Kawabata, T, Komocsar, W, Lotze, M, Nepom, J, Ochs, H, O'Lone, R, Phippard, D, Plevy, S, Rich, S, Roederer, M, Rotrosen, D, and Yeh, J-H. "A model for harmonizing flow cytometry in clinical trials." Nature Immunology 11.11 (2010): 975-978.
Website
http://hdl.handle.net/10161/14743
PMID
20959798
Source
scival
Published In
Nature Immunology
Volume
11
Issue
11
Publish Date
2010
Start Page
975
End Page
978
DOI
10.1038/ni1110-975

Polychromatic Flow Cytometry Identifies T Cell Subsets In Human Lung Transplant Recipients

Authors
Snyder, LD; Sparks, SD; Davis, WA; Medinas, R; Weinhold, KJ; Palmer, SM
MLA Citation
Snyder, LD, Sparks, SD, Davis, WA, Medinas, R, Weinhold, KJ, and Palmer, SM. "Polychromatic Flow Cytometry Identifies T Cell Subsets In Human Lung Transplant Recipients." 2010.
Source
wos-lite
Published In
American journal of respiratory and critical care medicine
Volume
181
Publish Date
2010

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

Polychromatic immunophenotypic characterization of T cell profiles among HIV-infected patients experiencing immune reconstitution inflammatory syndrome (IRIS).

OBJECTIVE: To immunophenotype CD4+ and CD8+ T cell sub-populations in HIV-associated immune reconstitution inflammatory syndrome (IRIS). DESIGN: Nested case-control immunological study. METHODS: ART-naïve HIV-infected patients were prospectively observed for IRIS during the first 6 months of ART. Twenty-two IRIS cases and 22 ART-duration matched controls were sampled for T cell immunophenotyping. RESULTS: IRIS cases demonstrated significantly lower CD4 cell counts compared to controls (baseline: 79 versus 142, p = 0.02; enrollment: 183 versus 263, p = 0.05, respectively) with no differences in HIV RNA levels. Within CD4+T cells, cases exhibited more of an effector memory phenotype compared to controls (40.8 versus 27.0%, p = 0.20), while controls trended towards a central memory phenotype (43.8 versus 30.8%, p = 0.07). Within CD8+ T cells, controls exhibited more central memory (13.9 versus 7.81%, p = 0.01, respectively) and effector (13.2 versus 8.8%, p = 0.04, respectively) phenotypes compared to cases, whereas cases demonstrated more terminal effectors than controls (28.8 versus 15.1%, p = 0.05). Cases demonstrated increased activation of CD8+ T cell effector memory, terminal effector, and effector subsets than controls (p = 0.04, 0.02, and 0.02, respectively). CONCLUSION: CD4+ and CD8+ T cell subset maturational phenotypes were heterogeneous among IRIS cases and controls. However, IRIS cases demonstrated significant increases in activation of CD8+ T cell effector subpopulations.

Authors
Murdoch, DM; Suchard, MS; Venter, WDF; Mhlangu, P; Ottinger, JS; Feldman, C; Van Rie, A; Glencross, DK; Stevens, WS; Weinhold, KJ
MLA Citation
Murdoch, DM, Suchard, MS, Venter, WDF, Mhlangu, P, Ottinger, JS, Feldman, C, Van Rie, A, Glencross, DK, Stevens, WS, and Weinhold, KJ. "Polychromatic immunophenotypic characterization of T cell profiles among HIV-infected patients experiencing immune reconstitution inflammatory syndrome (IRIS). (Published online)" AIDS Res Ther 6 (July 16, 2009): 16-.
PMID
19607684
Source
pubmed
Published In
AIDS Research and Therapy
Volume
6
Publish Date
2009
Start Page
16
DOI
10.1186/1742-6405-6-16

The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection.

Identification of the transmitted/founder virus makes possible, for the first time, a genome-wide analysis of host immune responses against the infecting HIV-1 proteome. A complete dissection was made of the primary HIV-1-specific T cell response induced in three acutely infected patients. Cellular assays, together with new algorithms which identify sites of positive selection in the virus genome, showed that primary HIV-1-specific T cells rapidly select escape mutations concurrent with falling virus load in acute infection. Kinetic analysis and mathematical modeling of virus immune escape showed that the contribution of CD8 T cell-mediated killing of productively infected cells was earlier and much greater than previously recognized and that it contributed to the initial decline of plasma virus in acute infection. After virus escape, these first T cell responses often rapidly waned, leaving or being succeeded by T cell responses to epitopes which escaped more slowly or were invariant. These latter responses are likely to be important in maintaining the already established virus set point. In addition to mutations selected by T cells, there were other selected regions that accrued mutations more gradually but were not associated with a T cell response. These included clusters of mutations in envelope that were targeted by NAbs, a few isolated sites that reverted to the consensus sequence, and bystander mutations in linkage with T cell-driven escape.

Authors
Goonetilleke, N; Liu, MKP; Salazar-Gonzalez, JF; Ferrari, G; Giorgi, E; Ganusov, VV; Keele, BF; Learn, GH; Turnbull, EL; Salazar, MG; Weinhold, KJ; Moore, S; CHAVI Clinical Core B, ; Letvin, N; Haynes, BF; Cohen, MS; Hraber, P; Bhattacharya, T; Borrow, P; Perelson, AS; Hahn, BH; Shaw, GM; Korber, BT; McMichael, AJ
MLA Citation
Goonetilleke, N, Liu, MKP, Salazar-Gonzalez, JF, Ferrari, G, Giorgi, E, Ganusov, VV, Keele, BF, Learn, GH, Turnbull, EL, Salazar, MG, Weinhold, KJ, Moore, S, CHAVI Clinical Core B, , Letvin, N, Haynes, BF, Cohen, MS, Hraber, P, Bhattacharya, T, Borrow, P, Perelson, AS, Hahn, BH, Shaw, GM, Korber, BT, and McMichael, AJ. "The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection." J Exp Med 206.6 (June 8, 2009): 1253-1272.
PMID
19487423
Source
pubmed
Published In
The Journal of Experimental Medicine
Volume
206
Issue
6
Publish Date
2009
Start Page
1253
End Page
1272
DOI
10.1084/jem.20090365

HIV Frequently Elicits Mucosal and Plasma Env-Specific IgA With a Rapid Initial Decline In Acute Infection

Authors
Yates, NL; Lucas, J; Parks, R; Ashley, VC; Overman, G; Montefiori, DC; Weinhold, KJ; Shattock, R; Cohen, M; Haynes, BF; Tomaras, GD; Team, CHAVI
MLA Citation
Yates, NL, Lucas, J, Parks, R, Ashley, VC, Overman, G, Montefiori, DC, Weinhold, KJ, Shattock, R, Cohen, M, Haynes, BF, Tomaras, GD, and Team, CHAVI. "HIV Frequently Elicits Mucosal and Plasma Env-Specific IgA With a Rapid Initial Decline In Acute Infection." June 2009.
Source
wos-lite
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
51
Publish Date
2009
Start Page
65
End Page
65
DOI
10.1097/01.qai.0000351099.78513.42

In vivo gp41 antibodies targeting the 2F5 monoclonal antibody epitope mediate human immunodeficiency virus type 1 neutralization breadth.

The broadly neutralizing human monoclonal antibodies (MAbs) 2F5 and 4E10, both targeting the highly conserved human immunodeficiency virus type 1 (HIV-1) envelope membrane proximal external region (MPER), are among the MAbs with the broadest heterologous neutralizing activity and are of considerable interest for HIV-1 vaccine development. We have identified serum antibodies from an HIV-infected subject that both were broadly neutralizing and specifically targeted MPER epitopes that overlap the 2F5 epitope. These MPER-specific antibodies were made 15 to 20 months following transmission and concomitantly with the development of autoantibodies. Our findings suggest that multiple events (i.e., genetic predisposition and HIV-1 immune dysregulation) may be required for induction of broadly reactive gp41 MPER antibodies in natural infection.

Authors
Shen, X; Parks, RJ; Montefiori, DC; Kirchherr, JL; Keele, BF; Decker, JM; Blattner, WA; Gao, F; Weinhold, KJ; Hicks, CB; Greenberg, ML; Hahn, BH; Shaw, GM; Haynes, BF; Tomaras, GD
MLA Citation
Shen, X, Parks, RJ, Montefiori, DC, Kirchherr, JL, Keele, BF, Decker, JM, Blattner, WA, Gao, F, Weinhold, KJ, Hicks, CB, Greenberg, ML, Hahn, BH, Shaw, GM, Haynes, BF, and Tomaras, GD. "In vivo gp41 antibodies targeting the 2F5 monoclonal antibody epitope mediate human immunodeficiency virus type 1 neutralization breadth." J Virol 83.8 (April 2009): 3617-3625.
PMID
19193787
Source
pubmed
Published In
Journal of virology
Volume
83
Issue
8
Publish Date
2009
Start Page
3617
End Page
3625
DOI
10.1128/JVI.02631-08

Safety and immunogenicity of a CTL multiepitope peptide vaccine for HIV with or without GM-CSF in a phase I trial.

There is an urgent need for a vaccine capable of preventing HIV infection or the development of HIV-related disease. A number of approaches designed to stimulate HIV-specific CD8+ cytotoxic T cell responses together with helper responses are presently under evaluation. In this phase 1, multi-center, placebo-controlled trial, we tested the ability of a novel multiepitope peptide vaccine to elicit HIV-specific immunity. To enhance the immunogenicity of the peptide vaccine, half of the vaccine recipients received recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) protein as a coadjuvant. The vaccine was safe; tolerability was moderate, with a number of adverse events related to local injection site reactogenicity. Anti-GM-CSF antibody responses developed in the majority of GM-CSF recipients but were not associated with adverse hematologic events. The vaccine was only minimally immunogenic. Six of 80 volunteers who received vaccine developed HIV-specific responses as measured by interferon-gamma ELISPOT assay, and measurable responses were transient. This study failed to demonstrate that GM-CSF can substantially improve the overall weak immunogenicity of a multiepitope peptide-based HIV vaccine.

Authors
Spearman, P; Kalams, S; Elizaga, M; Metch, B; Chiu, Y-L; Allen, M; Weinhold, KJ; Ferrari, G; Parker, SD; McElrath, MJ; Frey, SE; Fuchs, JD; Keefer, MC; Lubeck, MD; Egan, M; Braun, R; Eldridge, JH; Haynes, BF; Corey, L; NIAID HIV Vaccine Trials Network,
MLA Citation
Spearman, P, Kalams, S, Elizaga, M, Metch, B, Chiu, Y-L, Allen, M, Weinhold, KJ, Ferrari, G, Parker, SD, McElrath, MJ, Frey, SE, Fuchs, JD, Keefer, MC, Lubeck, MD, Egan, M, Braun, R, Eldridge, JH, Haynes, BF, Corey, L, and NIAID HIV Vaccine Trials Network, . "Safety and immunogenicity of a CTL multiepitope peptide vaccine for HIV with or without GM-CSF in a phase I trial." Vaccine 27.2 (January 7, 2009): 243-249.
PMID
18996425
Source
pubmed
Published In
Vaccine
Volume
27
Issue
2
Publish Date
2009
Start Page
243
End Page
249
DOI
10.1016/j.vaccine.2008.10.051

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "S01-04 OA. Phenotypic analyses of CD8+ T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+ virus controllers." October 22, 2009.
Source
scopus
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
O1

OA06-04. The role of early T-cell responses in subjects with acute HIV-1 infection

Authors
Liu, MK; Ferrari, G; Salazar, J; Keele, B; Tanner, RL; Hraber, P; Giorgi, E; Ganusov, VV; Learn, GH; Salazar, MG; Moore, SR; Digleria, K; Yu, Z; Rostron, T; DeBoer, C; Williams, A; Margaret, C; Kopycinski, J; Campion, SL; Bourne, VE; Brackenridge, S; Hahn, B; Cohen, M; Borrow, P; Weinhold, K; Perelson, A; Shaw, G; Korber, T; Goonetilleke, N; McMichael, AJ
MLA Citation
Liu, MK, Ferrari, G, Salazar, J, Keele, B, Tanner, RL, Hraber, P, Giorgi, E, Ganusov, VV, Learn, GH, Salazar, MG, Moore, SR, Digleria, K, Yu, Z, Rostron, T, DeBoer, C, Williams, A, Margaret, C, Kopycinski, J, Campion, SL, Bourne, VE, Brackenridge, S, Hahn, B, Cohen, M, Borrow, P, Weinhold, K, Perelson, A, Shaw, G, Korber, T, Goonetilleke, N, and McMichael, AJ. "OA06-04. The role of early T-cell responses in subjects with acute HIV-1 infection." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009

P01-05. Rapid perforin upregulation dominates the HIV-specific CD8 T cell response during acute HIV-infection

Authors
Makedonas, G; Frank, I; Guidonis, D; Ostrowski, MA; Weinhold, KJ; Betts, MR
MLA Citation
Makedonas, G, Frank, I, Guidonis, D, Ostrowski, MA, Weinhold, KJ, and Betts, MR. "P01-05. Rapid perforin upregulation dominates the HIV-specific CD8 T cell response during acute HIV-infection." 2009.
Source
scival
Published In
Retrovirology
Volume
6
Issue
SUPPL. 3
Publish Date
2009
Start Page
P5

Phenotypic analyses of CD8+T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+virus controllers

Authors
Freel, SA; Chattopadhyay, PK; Lamoreaux, L; Zarkowsky, D; Overman, RG; Ochsenbauer-Jambor, C; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Koup, RA; Graham, BS; Haynes, BF; Roederer, M; Tomaras, GD
MLA Citation
Freel, SA, Chattopadhyay, PK, Lamoreaux, L, Zarkowsky, D, Overman, RG, Ochsenbauer-Jambor, C, Kappes, JC, Cunningham, CK, Denny, TN, Weinhold, KJ, Ferrari, G, Koup, RA, Graham, BS, Haynes, BF, Roederer, M, and Tomaras, GD. "Phenotypic analyses of CD8+T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+virus controllers." 2009.
Source
wos-lite
Published In
Retrovirology
Volume
6
Publish Date
2009

Rapid perforin upregulation dominates the HIV-specific CD8 T cell response during acute HIV-infection

Authors
Makedonas, G; Frank, I; Guidonis, D; Ostrowski, MA; Weinhold, KJ; Betts, MR
MLA Citation
Makedonas, G, Frank, I, Guidonis, D, Ostrowski, MA, Weinhold, KJ, and Betts, MR. "Rapid perforin upregulation dominates the HIV-specific CD8 T cell response during acute HIV-infection." 2009.
Source
wos-lite
Published In
Retrovirology
Volume
6
Publish Date
2009

Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia.

A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus), but, to date, this period has been logistically difficult to analyze. To probe B-cell responses immediately following HIV-1 transmission, we have determined envelope-specific antibody responses to autologous and consensus Envs in plasma donors from the United States for whom frequent plasma samples were available at time points immediately before, during, and after HIV-1 plasma viral load (VL) ramp-up in acute infection, and we have modeled the antibody effect on the kinetics of plasma viremia. The first detectable B-cell response was in the form of immune complexes 8 days after plasma virus detection, whereas the first free plasma anti-HIV-1 antibody was to gp41 and appeared 13 days after the appearance of plasma virus. In contrast, envelope gp120-specific antibodies were delayed an additional 14 days. Mathematical modeling of the earliest viral dynamics was performed to determine the impact of antibody on HIV replication in vivo as assessed by plasma VL. Including the initial anti-gp41 immunoglobulin G (IgG), IgM, or both responses in the model did not significantly impact the early dynamics of plasma VL. These results demonstrate that the first IgM and IgG antibodies induced by transmitted HIV-1 are capable of binding virions but have little impact on acute-phase viremia at the timing and magnitude that they occur in natural infection.

Authors
Tomaras, GD; Yates, NL; Liu, P; Qin, L; Fouda, GG; Chavez, LL; Decamp, AC; Parks, RJ; Ashley, VC; Lucas, JT; Cohen, M; Eron, J; Hicks, CB; Liao, H-X; Self, SG; Landucci, G; Forthal, DN; Weinhold, KJ; Keele, BF; Hahn, BH; Greenberg, ML; Morris, L; Karim, SSA; Blattner, WA; Montefiori, DC; Shaw, GM; Perelson, AS; Haynes, BF
MLA Citation
Tomaras, GD, Yates, NL, Liu, P, Qin, L, Fouda, GG, Chavez, LL, Decamp, AC, Parks, RJ, Ashley, VC, Lucas, JT, Cohen, M, Eron, J, Hicks, CB, Liao, H-X, Self, SG, Landucci, G, Forthal, DN, Weinhold, KJ, Keele, BF, Hahn, BH, Greenberg, ML, Morris, L, Karim, SSA, Blattner, WA, Montefiori, DC, Shaw, GM, Perelson, AS, and Haynes, BF. "Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia." J Virol 82.24 (December 2008): 12449-12463.
PMID
18842730
Source
pubmed
Published In
Journal of virology
Volume
82
Issue
24
Publish Date
2008
Start Page
12449
End Page
12463
DOI
10.1128/JVI.01708-08

SIMPLIFIED METHOD TO OPTIMIZE REAGENTS FOR AN 11-COLOR (13-MARKER) POLYCHROMATIC INTRACELLULAR STAINING (ICS) PANEL

Authors
Ottinger, JS; Mensali, N; Jennifer, E; Weinhold, AK; Weinhold, KJ
MLA Citation
Ottinger, JS, Mensali, N, Jennifer, E, Weinhold, AK, and Weinhold, KJ. "SIMPLIFIED METHOD TO OPTIMIZE REAGENTS FOR AN 11-COLOR (13-MARKER) POLYCHROMATIC INTRACELLULAR STAINING (ICS) PANEL." November 2008.
Source
wos-lite
Published In
Cytometry
Volume
74B
Issue
6
Publish Date
2008
Start Page
373
End Page
373

Induction of plasma (TRAIL), TNFR-2, Fas ligand, and plasma microparticles after human immunodeficiency virus type 1 (HIV-1) transmission: implications for HIV-1 vaccine design.

The death of CD4(+) CCR5(+) T cells is a hallmark of human immunodeficiency virus (HIV) infection. We studied the plasma levels of cell death mediators and products--tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), Fas ligand, TNF receptor type 2 (TNFR-2), and plasma microparticles--during the earliest stages of infection following HIV type 1 (HIV-1) transmission in plasma samples from U.S. plasma donors. Significant plasma TRAIL level elevations occurred a mean of 7.2 days before the peak of plasma viral load (VL), while TNFR-2, Fas ligand, and microparticle level elevations occurred concurrently with maximum VL. Microparticles had been previously shown to mediate immunosuppressive effects on T cells and macrophages. We found that T-cell apoptotic microparticles also potently suppressed in vitro immunoglobulin G (IgG) and IgA antibody production by memory B cells. Thus, release of TRAIL during the onset of plasma viremia (i.e., the eclipse phase) in HIV-1 transmission may initiate or amplify early HIV-1-induced cell death. The window of opportunity for a HIV-1 vaccine is from the time of HIV-1 transmission until establishment of the latently infected CD4(+) T cells. Release of products of cell death and subsequent immunosuppression following HIV-1 transmission could potentially narrow the window of opportunity during which a vaccine is able to extinguish HIV-1 infection and could place severe constraints on the amount of time available for the immune system to respond to the transmitted virus.

Authors
Gasper-Smith, N; Crossman, DM; Whitesides, JF; Mensali, N; Ottinger, JS; Plonk, SG; Moody, MA; Ferrari, G; Weinhold, KJ; Miller, SE; Reich, CF; Qin, L; Self, SG; Shaw, GM; Denny, TN; Jones, LE; Pisetsky, DS; Haynes, BF
MLA Citation
Gasper-Smith, N, Crossman, DM, Whitesides, JF, Mensali, N, Ottinger, JS, Plonk, SG, Moody, MA, Ferrari, G, Weinhold, KJ, Miller, SE, Reich, CF, Qin, L, Self, SG, Shaw, GM, Denny, TN, Jones, LE, Pisetsky, DS, and Haynes, BF. "Induction of plasma (TRAIL), TNFR-2, Fas ligand, and plasma microparticles after human immunodeficiency virus type 1 (HIV-1) transmission: implications for HIV-1 vaccine design." J Virol 82.15 (August 2008): 7700-7710.
PMID
18508902
Source
pubmed
Published In
Journal of virology
Volume
82
Issue
15
Publish Date
2008
Start Page
7700
End Page
7710
DOI
10.1128/JVI.00605-08

Safety and immunogenicity of cytotoxic T-lymphocyte poly-epitope, DNA plasmid (EP HIV-1090) vaccine in healthy, human immunodeficiency virus type 1 (HIV-1)-uninfected adults.

We evaluated EP HIV-1090 vaccine, a DNA plasmid encoding 21 cytotoxic T-lymphocyte (CTL) epitopes of human immunodeficiency virus type 1 (HIV-1) and the pan-DR helper T-lymphocyte epitope (PADRE), in a dose escalation, randomized, double-blinded, placebo-controlled Phase 1 trial. Vaccine, at 0.5, 2.0, or 4.0mg doses, or placebo was injected four times over 6 months. Forty-two healthy, HIV-1-uninfected adults were enrolled. Using an interferon-gamma ELISPOT assay, a response to PADRE was detected in one vaccine recipient. Three vaccine recipients raised anti-HIV-1 CD8+ CTL measured by chromium-release assay. The vaccine was safe and well-tolerated, but only weakly immunogenic.

Authors
Gorse, GJ; Baden, LR; Wecker, M; Newman, MJ; Ferrari, G; Weinhold, KJ; Livingston, BD; Villafana, TL; Li, H; Noonan, E; Russell, ND; HIV Vaccine Trials Network,
MLA Citation
Gorse, GJ, Baden, LR, Wecker, M, Newman, MJ, Ferrari, G, Weinhold, KJ, Livingston, BD, Villafana, TL, Li, H, Noonan, E, Russell, ND, and HIV Vaccine Trials Network, . "Safety and immunogenicity of cytotoxic T-lymphocyte poly-epitope, DNA plasmid (EP HIV-1090) vaccine in healthy, human immunodeficiency virus type 1 (HIV-1)-uninfected adults." Vaccine 26.2 (January 10, 2008): 215-223.
PMID
18055072
Source
pubmed
Published In
Vaccine
Volume
26
Issue
2
Publish Date
2008
Start Page
215
End Page
223
DOI
10.1016/j.vaccine.2007.10.061

Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection.

Two human monoclonal antibodies (MAbs) (2F5 and 4E10) against the human immunodeficiency virus type 1 (HIV-1) envelope g41 cluster II membrane proximal external region (MPER) broadly neutralize HIV-1 primary isolates. However, these antibody specificities are rare, are not induced by Env immunization or HIV-1 infection, and are polyspecific and also react with lipids such as cardiolipin or phosphatidylserine. To probe MPER anti-gp41 antibodies that are produced in HIV-1 infection, we have made two novel murine MAbs, 5A9 and 13H11, against HIV-1 gp41 envelope that partially cross-blocked 2F5 MAb binding to Env but did not neutralize HIV-1 primary isolates or bind host lipids. Competitive inhibition assays using labeled 13H11 MAb and HIV-1-positive patient plasma samples demonstrated that cluster II 13H11-blocking plasma antibodies were made in 83% of chronically HIV-1 infected patients and were acquired between 5 to 10 weeks after acute HIV-1 infection. Both the mouse 13H11 MAb and the three prototypic cluster II human MAbs (98-6, 126-6, and 167-D) blocked 2F5 binding to gp41 epitopes to variable degrees; the combination of 98-6 and 13H11 completely blocked 2F5 binding. These data provide support for the hypothesis that in some patients, B cells make nonneutralizing cluster II antibodies that may mask or otherwise down-modulate B-cell responses to immunogenic regions of gp41 that could be recognized by B cells capable of producing antibodies like 2F5.

Authors
Alam, SM; Scearce, RM; Parks, RJ; Plonk, K; Plonk, SG; Sutherland, LL; Gorny, MK; Zolla-Pazner, S; Vanleeuwen, S; Moody, MA; Xia, S-M; Montefiori, DC; Tomaras, GD; Weinhold, KJ; Karim, SA; Hicks, CB; Liao, H-X; Robinson, J; Shaw, GM; Haynes, BF
MLA Citation
Alam, SM, Scearce, RM, Parks, RJ, Plonk, K, Plonk, SG, Sutherland, LL, Gorny, MK, Zolla-Pazner, S, Vanleeuwen, S, Moody, MA, Xia, S-M, Montefiori, DC, Tomaras, GD, Weinhold, KJ, Karim, SA, Hicks, CB, Liao, H-X, Robinson, J, Shaw, GM, and Haynes, BF. "Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection." J Virol 82.1 (January 2008): 115-125.
PMID
17942537
Source
pubmed
Published In
Journal of virology
Volume
82
Issue
1
Publish Date
2008
Start Page
115
End Page
125
DOI
10.1128/JVI.00927-07

Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: negative results fail to trigger a phase 3 correlates trial.

BACKGROUND: A goal of T-cell HIV vaccines is to define the correlation between a vaccine-induced immune response and protection from HIV infection. We conducted a phase 2 trial to determine if a canarypox vaccine candidate (vCP1452) administered with rgp120 subunit protein would "qualify" for a trial to define a correlate of efficacy. METHODS: A total of 330 healthy volunteers were enrolled into 4 groups: 120 received vCP1452 alone (0, 1, 3, and 6 months), 120 received vCP1452 with 2 different regimens of rgp120 coadministration, and 90 received placebo. HIV-specific antibody responses were measured by enzyme-linked immunoassay (ELISA) and neutralizing activity. T-cell responses were measured by chromium release and interferon-gamma (IFNgamma) enzyme-linked immunospot (ELISpot) assay. RESULTS: Significant neutralizing antibody responses to the HIV MN strain were detected in all vaccine groups, with net responses ranging from 57% (95% confidence interval [CI]: 40% to 71%) to 94% (95% CI: 85% to 99%). Net cumulative HIV-specific CD8 IFNgamma ELISpot assay responses were 13% (95% CI: -1% to 26%) for recipients of vCP1452 alone and 16% (95% CI: 2% to 29%) for recipients of vCP1452 plus rgp120. CONCLUSIONS: Overall, the HIV-specific CD8 cytotoxic T lymphocyte (CTL) response was not sufficient to qualify the regimen for a subsequent trial designed to detect an immune correlate of protection requiring a minimum CD8 CTL frequency of 30%.

Authors
Russell, ND; Graham, BS; Keefer, MC; McElrath, MJ; Self, SG; Weinhold, KJ; Montefiori, DC; Ferrari, G; Horton, H; Tomaras, GD; Gurunathan, S; Baglyos, L; Frey, SE; Mulligan, MJ; Harro, CD; Buchbinder, SP; Baden, LR; Blattner, WA; Koblin, BA; Corey, L; National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network,
MLA Citation
Russell, ND, Graham, BS, Keefer, MC, McElrath, MJ, Self, SG, Weinhold, KJ, Montefiori, DC, Ferrari, G, Horton, H, Tomaras, GD, Gurunathan, S, Baglyos, L, Frey, SE, Mulligan, MJ, Harro, CD, Buchbinder, SP, Baden, LR, Blattner, WA, Koblin, BA, Corey, L, and National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network, . "Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: negative results fail to trigger a phase 3 correlates trial." J Acquir Immune Defic Syndr 44.2 (February 1, 2007): 203-212.
PMID
17106277
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
44
Issue
2
Publish Date
2007
Start Page
203
End Page
212
DOI
10.1097/01.qai.0000248356.48501.ff

Phase 1 clinical trials of the National Institutes of Health Vaccine Research Center HIV/AIDS candidate vaccines.

Authors
Robinson, HL; Weinhold, KJ
MLA Citation
Robinson, HL, and Weinhold, KJ. "Phase 1 clinical trials of the National Institutes of Health Vaccine Research Center HIV/AIDS candidate vaccines." J Infect Dis 194.12 (December 15, 2006): 1625-1627.
PMID
17109331
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
194
Issue
12
Publish Date
2006
Start Page
1625
End Page
1627
DOI
10.1086/509263

Excellent safety and tolerability of the human immunodeficiency virus type 1 pGA2/JS2 plasmid DNA priming vector vaccine in HIV type 1 uninfected adults.

A vaccine consisting of DNA priming followed by recombinant modified vaccinia Ankara (rMVA) boosting has achieved long-term control of a pathogenic challenge with a chimera of simian and human immunodeficiency viruses (SHIV-89.6P) in rhesus macaques. Based on these results, clade B HIV-1 DNA and rMVA immunogens have been developed for trials in humans. We conducted a first-time in humans phase I safety trial using the pGA2/JS2 (JS2) HIV-1 DNA priming vector expressing Gag, Pol, Env, Tat, Rev, and Vpu. Thirty HIV-uninfected adults were vaccinated with 0.3 or 3 mg of JS2 DNA, or a saline placebo, by intramuscular injection at months 0 and 2. Both doses of DNA were safe and well-tolerated with no differences between the control, 0.3 mg, or 3 mg groups (n = 6, 12, and 12, respectively) through 12 months of postvaccination follow- up. A chromium-release assay using fresh peripheral blood mononuclear cells (PBMCs) and a validated IFN-gamma ELISpot assay with frozen PBMCs failed to detect CD4(+) or CD8(+) HIV-1-specific T cell responses. HIV-specific neutralizing antibodies were also not detected. The vaccine is being further developed as a priming vector for a combined DNA plus rMVA prime/boost HIV vaccination regimen.

Authors
Mulligan, MJ; Russell, ND; Celum, C; Kahn, J; Noonan, E; Montefiori, DC; Ferrari, G; Weinhold, KJ; Smith, JM; Amara, RR; Robinson, HL; NIH/NIAID/DAIDS HIV Vaccine Trials Network,
MLA Citation
Mulligan, MJ, Russell, ND, Celum, C, Kahn, J, Noonan, E, Montefiori, DC, Ferrari, G, Weinhold, KJ, Smith, JM, Amara, RR, Robinson, HL, and NIH/NIAID/DAIDS HIV Vaccine Trials Network, . "Excellent safety and tolerability of the human immunodeficiency virus type 1 pGA2/JS2 plasmid DNA priming vector vaccine in HIV type 1 uninfected adults." AIDS Res Hum Retroviruses 22.7 (July 2006): 678-683.
PMID
16831092
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
22
Issue
7
Publish Date
2006
Start Page
678
End Page
683
DOI
10.1089/aid.2006.22.678

Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection.

Worldwide HIV-1 vaccine efforts are guided by the principle that HIV-specific T cell responses may provide protection from infection or delay overt disease. However, no clear correlates of T cell-mediated immune protection have been identified. Here, we examine in a HLA-B27(+) HIV seronegative vaccinee persistent HIV-specific vaccine-induced anti-Gag CD4(+) and CD8(+) T cell responses. Although these responses exhibited those characteristics (multifunctionality, appropriate memory phenotype, and targeting of epitopes associated with long-term nonprogression) predicted to correlate with protection from infection, the subject became HIV infected. After HIV infection, the vaccine-induced CD8(+) T cells expanded, but both CD4(+) and CD8(+) T cell responses acquired the functional and phenotypic patterns characteristic of chronic HIV infection. The virus quickly escaped the vaccine-induced T cell response, and the subject progressed more rapidly than expected for someone expressing the HLA-B27 allele. These data suggest that control of HIV by vaccine-elicited HIV-specific T cell responses may be difficult, even when the T cell response has those characteristics predicted to provide optimal protection.

Authors
Betts, MR; Exley, B; Price, DA; Bansal, A; Camacho, ZT; Teaberry, V; West, SM; Ambrozak, DR; Tomaras, G; Roederer, M; Kilby, JM; Tartaglia, J; Belshe, R; Gao, F; Douek, DC; Weinhold, KJ; Koup, RA; Goepfert, P; Ferrari, G
MLA Citation
Betts, MR, Exley, B, Price, DA, Bansal, A, Camacho, ZT, Teaberry, V, West, SM, Ambrozak, DR, Tomaras, G, Roederer, M, Kilby, JM, Tartaglia, J, Belshe, R, Gao, F, Douek, DC, Weinhold, KJ, Koup, RA, Goepfert, P, and Ferrari, G. "Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection." Proc Natl Acad Sci U S A 102.12 (March 22, 2005): 4512-4517.
PMID
15753288
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
102
Issue
12
Publish Date
2005
Start Page
4512
End Page
4517
DOI
10.1073/pnas.0408773102

Longitudinal assessment of immune response and viral characteristics in HIV-infected patients with prolonged CD4(+)/viral load discordance.

Although suppression of HIV-1 RNA below the limit of detection is associated with optimal outcomes, many patients can maintain or increase their CD4(+) count for prolonged time periods in the presence of persistent low-level viremia. We followed seven patients with prolonged (>5 years) discordant CD4(+)/viral load (VL) responses on protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) prospectively for 1 year to assess evolution of immune function, viral phenotype, replication capacity (RC), and resistance profile. Immune function was assessed by qualitative and quantitative measurement of cellular activation (CD38(+)HLA-DR(+) and CD38 antibodies bound per cell), and the interferon (IFN)-() ELISpot assay. Presence of syncytium-inducing (SI) or nonsyncytium-inducing (NSI) viral strains was determined by MT-2 cell culture. RC was measured by a modified rapid recombinant virus assay. The resistance profile was characterized by both genotypic and phenotypic analysis. Over the year of follow-up, IFN-() production to gag persisted, responses to other HIV antigens increased, and markers of cellular activation did not change. NSI virus predominated. The genotypic (GSS) and phenotypic (PSS) susceptibility scores remained stable. Evolution of RC was variable over the year of follow-up, but the RC of viruses remained well below that of wild-type clinical isolates. Thus, CD4(+)/VL discordance can be maintained for periods exceeding 5 years in some patients receiving PI-based HAART without significant evolution of HIV resistance.

Authors
Kaplan, SS; Ferrari, G; Wrin, T; Hellmann, NS; Tomaras, GD; Gryszowka, VE; Fiscus, SA; Weinhold, KJ; Hicks, CB
MLA Citation
Kaplan, SS, Ferrari, G, Wrin, T, Hellmann, NS, Tomaras, GD, Gryszowka, VE, Fiscus, SA, Weinhold, KJ, and Hicks, CB. "Longitudinal assessment of immune response and viral characteristics in HIV-infected patients with prolonged CD4(+)/viral load discordance." AIDS Res Hum Retroviruses 21.1 (January 2005): 13-16.
PMID
15665640
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
21
Issue
1
Publish Date
2005
Start Page
13
End Page
16
DOI
10.1089/aid.2005.21.13

Standardization of cytokine flow cytometry assays

Background: Cytokine flow cytometry (CFC) or intracellular cytokine staining (ICS) can quantitate antigen-specific T cell responses in settings such as experimental vaccination. Standardization of ICS among laboratories performing vaccine studies would provide a common platform by which to compare the immunogenicity of different vaccine candidates across multiple international organizations conducting clinical trials. As such, a study was carried out among several laboratories involved in HIV clinical trials, to define the inter-lab precision of ICS using various sample types, and using a common protocol for each experiment (see additional files online). Results: Three sample types (activated, fixed, and frozen whole blood; fresh whole blood; and cryopreserved PBMC) were shipped to various sites, where ICS assays using cytomegalovirus (CMV) pp65 peptide mix or control antigens were performed in parallel in 96-well plates. For one experiment, antigens and antibody cocktails were lyophilised into 96-well plates to simplify and standardize the assay setup. Results (CD4+cytokine+ cells and CD8+cytokine+ cells) were determined by each site. Raw data were also sent to a central site for batch analysis with a dynamic gating template. Mean inter-laboratory coefficient of variation (C.V.) ranged from 17-44% depending upon the sample type and analysis method. Cryopreserved peripheral blood mononuclear cells (PBMC) yielded lower inter-lab C.V.'s than whole blood. Centralized analysis (using a dynamic gating template) reduced the inter-lab C.V. by 5-20%, depending upon the experiment. The inter-lab C.V. was lowest (18-24%) for samples with a mean of >0.5% IFNγ + T cells, and highest (57-82%) for samples with a mean of <0.1% IFNγ + cells. Conclusion: ICS assays can be performed by multiple laboratories using a common protocol with good inter-laboratory precision, which improves as the frequency of responding cells increases. Cryopreserved PBMC may yield slightly more consistent results than shipped whole blood. Analysis, particularly gating, is a significant source of variability, and can be reduced by centralized analysis and/or use of a standardized dynamic gating template. Use of pre-ali quoted lyophilized reagents for stimulation and staining can provide further standardization to these assays. © 2005 Maecker et al; licensee BioMed Central Ltd.

Authors
Maecker, HT; Rinfret, A; D'Souza, P; Darden, J; Roig, E; Landry, C; Hayes, P; Birungi, J; Anzala, O; Garcia, M; Harari, A; Frank, I; Baydo, R; Baker, M; Holbrook, J; Ottinger, J; Lamoreaux, L; Epling, CL; Sinclair, E; Suni, MA; Punt, K; Calarota, S; El-Bahi, S; Alter, G; Maila, H; Kuta, E; Cox, J; Gray, C; Altfeld, M; Nougarede, N; Boyer, J; Tussey, L; Tobery, T; Bredt, B; Roederer, M; Koup, R; Maino, VC; Weinhold, K; Pantaleo, G; Gilmour, J; Horton, H; Sekaly, RP
MLA Citation
Maecker, HT, Rinfret, A, D'Souza, P, Darden, J, Roig, E, Landry, C, Hayes, P, Birungi, J, Anzala, O, Garcia, M, Harari, A, Frank, I, Baydo, R, Baker, M, Holbrook, J, Ottinger, J, Lamoreaux, L, Epling, CL, Sinclair, E, Suni, MA, Punt, K, Calarota, S, El-Bahi, S, Alter, G, Maila, H, Kuta, E, Cox, J, Gray, C, Altfeld, M, Nougarede, N, Boyer, J, Tussey, L, Tobery, T, Bredt, B, Roederer, M, Koup, R, Maino, VC, Weinhold, K, Pantaleo, G, Gilmour, J, Horton, H, and Sekaly, RP. "Standardization of cytokine flow cytometry assays." BMC Immunology 6 (2005).
PMID
15978127
Source
scival
Published In
BMC Immunology
Volume
6
Publish Date
2005
DOI
10.1186/1471-2172-6-13

Demographic factors that influence the neutralizing antibody response in recipients of recombinant HIV-1 gp120 vaccines.

We compared neutralizing antibody responses in human immunodeficiency virus (HIV) type 1 gp120 vaccine recipients by age, sex, and race. Four phase 1 or 2 trials involving 505 vaccinated subjects were analyzed. Age and sex had no detectable effect on neutralizing antibody responses. However, race influenced the response to one vaccine, MN gp120, in alum. Four inoculations with this vaccine generated higher serum titers of neutralizing antibodies in African Americans than in whites. Despite potent neutralization of T cell line-adapted HIV-1, serum from these African Americans failed to neutralize primary HIV-1 isolates. Neutralizing antibody responses did not differ between races when SF2 gp120 in MF-59 was administered either alone or with recombinant canarypox vCP205; they also did not differ when vCP1452 was administered either alone or with AIDSVAX B/B in alum. These data indicate that race may affect the neutralizing antibody response to some gp120 immunogens. To fully evaluate immunogenicity, clinical trials of candidate vaccines should enroll diverse populations of subjects.

Authors
Montefiori, DC; Metch, B; McElrath, MJ; Self, S; Weinhold, KJ; Corey, L; HIV Vaccine Trials Network,
MLA Citation
Montefiori, DC, Metch, B, McElrath, MJ, Self, S, Weinhold, KJ, Corey, L, and HIV Vaccine Trials Network, . "Demographic factors that influence the neutralizing antibody response in recipients of recombinant HIV-1 gp120 vaccines." J Infect Dis 190.11 (December 1, 2004): 1962-1969.
PMID
15529261
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
190
Issue
11
Publish Date
2004
Start Page
1962
End Page
1969
DOI
10.1086/425518

Absence of immunodominant anti-Gag p17 (SL9) responses among Gag CTL-positive, HIV-uninfected vaccine recipients expressing the HLA-A*0201 allele.

According to a number of previous reports, control of HIV replication in humans appears to be linked to the presence of anti-HIV-1 Gag-specific CD8 responses. During the chronic phase of HIV-1 infection, up to 75% of the HIV-infected individuals who express the histocompatibility leukocyte Ag (HLA)-A*0201 recognize the Gag p17 SLYNTVATL (aa residues 77-85) epitope (SL9). However, the role of the anti-SL9 CD8 CTL in controlling HIV-1 infection remains controversial. In this study we determined whether the pattern of SL9 immunodominance in uninfected, HLA-A*0201 HIV vaccine recipients is similar to that seen in chronically HIV-infected subjects. The presence of anti-SL9 responses was determined using a panel of highly sensitive cellular immunoassays, including peptide:MHC tetramer binding, IFN-gamma ELISPOT, and cytokine flow cytometry. Thirteen HLA-A*0201 vaccinees with documented anti-Gag CD8 CTL reactivities were tested, and none had a detectable anti-SL9 response. These findings strongly suggest that the pattern of SL9 epitope immunodominance previously reported among chronically infected, HLA-A*0201-positive patients is not recapitulated in noninfected recipients of Gag-containing canarypox-based candidate vaccines and may be influenced by the relative immunogenicity of these constructs.

Authors
Ferrari, G; Neal, W; Ottinger, J; Jones, AM; Edwards, BH; Goepfert, P; Betts, MR; Koup, RA; Buchbinder, S; McElrath, MJ; Tartaglia, J; Weinhold, KJ
MLA Citation
Ferrari, G, Neal, W, Ottinger, J, Jones, AM, Edwards, BH, Goepfert, P, Betts, MR, Koup, RA, Buchbinder, S, McElrath, MJ, Tartaglia, J, and Weinhold, KJ. "Absence of immunodominant anti-Gag p17 (SL9) responses among Gag CTL-positive, HIV-uninfected vaccine recipients expressing the HLA-A*0201 allele." J Immunol 173.3 (August 1, 2004): 2126-2133.
PMID
15265949
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
173
Issue
3
Publish Date
2004
Start Page
2126
End Page
2133

HLA-A and -B allele expression and ability to develop anti-Gag cross-clade responses in subtype C HIV-1-infected Ethiopians.

A cohort of 35 human immunodeficiency virus type 1 (HIV-1) subtype C-infected Ethiopians was studied to define the HLA phenotype in all 35 subjects and highly conserved Gag protein regions involved in cross-clade cell-mediated immunity. Full-length Gag virus sequences were determined in 15 individuals. CD8 cell-mediated immune responses were detected by interferon-gamma ELISpot assay. HLA-A*03, -B*49, and -B*57 allelic frequencies were relatively higher than in other African populations. Anti-p17 (aa 1-60) CD8+ were detectable in the highest number of individuals. Anti-p17 (aa 1-60 and 51-110) cross-clade responses against subtype B and C were detected in 50% of the tested subjects. The p24 KF11 (aa 162-172) epitope was found to be immunodominant among the HLA-B*5703--positive individuals. These data represent the first report of correlating HLA phenotype and HIV-specific cell-mediated immune responses among infected Ethiopians and may be useful in designing cytotoxic T lymphocyte-inducing vaccines for this part of Africa.

Authors
Ferrari, G; Currier, JR; Harris, ME; Finkelstein, S; de Oliveira, A; Barkhan, D; Cox, JH; Zeira, M; Weinhold, KJ; Reinsmoen, N; McCutchan, F; Birx, DL; Osmanov, S; Maayan, S
MLA Citation
Ferrari, G, Currier, JR, Harris, ME, Finkelstein, S, de Oliveira, A, Barkhan, D, Cox, JH, Zeira, M, Weinhold, KJ, Reinsmoen, N, McCutchan, F, Birx, DL, Osmanov, S, and Maayan, S. "HLA-A and -B allele expression and ability to develop anti-Gag cross-clade responses in subtype C HIV-1-infected Ethiopians." Hum Immunol 65.6 (June 2004): 648-659.
PMID
15219385
Source
pubmed
Published In
Human Immunology
Volume
65
Issue
6
Publish Date
2004
Start Page
648
End Page
659
DOI
10.1016/j.humimm.2004.02.031

Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein.

BACKGROUND: Since the primary routes of human immunodeficiency type 1 (HIV-1) infection are across mucosal barriers, a randomized trial of canarypox virus-based vectors was conducted in 84 individuals, with delivery of vaccine by mucosal routes, and was accompanied by a detailed analysis of humoral, cellular, and mucosal immune responses. METHODS: Over the course of 6 months, HIV-1-specific (vCP 205) and rabies (vCP 65) canarypox virus vectors were delivered systemically and/or mucosally into the nose, mouth, vagina, or rectum in a 4-dose schedule, followed by 2 doses of HIV-1 MN recombinant glycoprotein (rgp) 120 or subunit rabies vaccine administered by the intramuscular route. RESULTS: Administration of vaccine and collection of samples were well tolerated. Serum IgG HIV-1-specific antibodies to rgp120 were rarely seen after either systemic or mucosal delivery of canarypox virus vaccine. In contrast, serum IgG rabies and canarypox antibodies were detected in all individuals after systemic, but rarely after mucosal, delivery of vaccine. Suggestions of mucosal recognition of HIV-1 antigen included a cytotoxic T lymphocyte response in 4 of 8 individuals after administration of vaccine by the intrarectal route and a limited immunoglobulin A response at the same site. CONCLUSIONS: Each of the routes of vaccine administration was feasible in the context of a phase 1 study with motivated individuals. However, with the doses and routes of administration used, canarypox virus was not an effective mucosal immunogen.

Authors
Wright, PF; Mestecky, J; McElrath, MJ; Keefer, MC; Gorse, GJ; Goepfert, PA; Moldoveanu, Z; Schwartz, D; Spearman, PW; El Habib, R; Spring, MD; Zhu, Y; Smith, C; Flores, J; Weinhold, KJ; National Institutes of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group,
MLA Citation
Wright, PF, Mestecky, J, McElrath, MJ, Keefer, MC, Gorse, GJ, Goepfert, PA, Moldoveanu, Z, Schwartz, D, Spearman, PW, El Habib, R, Spring, MD, Zhu, Y, Smith, C, Flores, J, Weinhold, KJ, and National Institutes of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group, . "Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein." J Infect Dis 189.7 (April 1, 2004): 1221-1231.
PMID
15031791
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
189
Issue
7
Publish Date
2004
Start Page
1221
End Page
1231
DOI
10.1086/382088

Rapid clearance of virus after acute HIV-1 infection: Correlates of risk of AIDS

Objective. Our objective was to define early virologie and immunologic determinants of human immunodeficiency virus (HIV) type 1 disease progression among 22 case subjects with acute infection from the Trinidad Seroconvertor Cohort. Methods. A linear segmented regression model was fitted to sequential quantitative virus load measurements. Parameters of virus kinetics during different phases of primary infection were correlated with clinical and immunologic end points, by use of Kaplan-Meier estimates and Cox regression. Results. Ten individuals developed acquired immunodeficiency syndrome (AIDS)-defining events. In univariate analysis, progression to AIDS was associated with rate of initial HIV clearance (P = .002), virus load during set point (P = .008), and CD4+ cell count during steady state (P = .04). In the multivariate analysis, a rapid rate of initial clearance was the sole independent predictor of subsequent progression to AIDS and was associated with a 92% reduction in the risk of AIDS. The rate of initial clearance is inversely correlated with the number of early symptoms (r = -0.66; P = .0008). However, symptoms did not predict subsequent risk of AIDS. Conclusion. Among a subset of patients, rapid clearance of plasma HIV-1 after peak viremia is associated with lower viral set point, prolonged virus suppression before loss of virologie control, and decreased risk of AIDS. These findings are consistent with the hypothesis that effective immune responses during the earliest phase of infection are important determinants of the subsequent natural history.

Authors
Blattner, WA; Oursler, KA; Cleghorn, F; Charurat, M; Sill, A; Bartholomew, C; Jack, N; O'Brien, T; Edwards, J; Tomaras, G; Weinhold, K; Greenberg, M
MLA Citation
Blattner, WA, Oursler, KA, Cleghorn, F, Charurat, M, Sill, A, Bartholomew, C, Jack, N, O'Brien, T, Edwards, J, Tomaras, G, Weinhold, K, and Greenberg, M. "Rapid clearance of virus after acute HIV-1 infection: Correlates of risk of AIDS." Journal of Infectious Diseases 189.10 (2004): 1793-1801.
PMID
15122515
Source
scival
Published In
Journal of Infectious Diseases
Volume
189
Issue
10
Publish Date
2004
Start Page
1793
End Page
1801
DOI
10.1086/386306

Correlation between interferon-γ secretion and cytotoxicity, in virus-specific memory T cells

ELISpot and intracellular cytokine staining are replacing the traditional cytolytic (51Cr release) assay method in vaccine trials using human immunodeficiency virus (HIV)-1, and it is widely assumed that the number of interferon (IFN)-γ-secreting T cells is a surrogate for the level of cytolytic activity. Thus, we sought to determine whether the detection of IFN-γ in CD8+ T cells correlates with cytolytic ability in vitro. In 29 (69.0%) of 42 HIV-1-seronegative immunocompetent individuals (22 unvaccinated and 20 vaccinated), virus-specific T cell responses recognizing cytomegalovirus, Epstein-Barr virus, and influenza and HIV-1 Gag epitopes were detected by at least 1 assay method (ELISpot, intracellular cytokine staining, and/or 51Cr release), and 18 (62.1%) of these 29 demonstrated both IFN-γ secretion and cytolysis. There was strong correlation between the results of IFN-γ ELISpot and those of IFN-γ intracellular cytokine staining (p = 0.88) and between the results of 51Cr release and those of intracellular cytokine staining (p = 0.81); although the correlation is not absolute, intracellular cytokine staining can be used - and is superior to ELISpot - as a surrogate for cytolytic assays.

Authors
Horton, H; Russell, N; Moore, E; Frank, I; Baydo, R; Havenar-Daughton, C; Lee, D; Deers, M; Hudgens, M; Weinhold, K; McElrath, MJ
MLA Citation
Horton, H, Russell, N, Moore, E, Frank, I, Baydo, R, Havenar-Daughton, C, Lee, D, Deers, M, Hudgens, M, Weinhold, K, and McElrath, MJ. "Correlation between interferon-γ secretion and cytotoxicity, in virus-specific memory T cells." Journal of Infectious Diseases 190.9 (2004): 1692-1696.
PMID
15478077
Source
scival
Published In
Journal of Infectious Diseases
Volume
190
Issue
9
Publish Date
2004
Start Page
1692
End Page
1696
DOI
10.1086/424490

Prolonged CD4+ cell/virus load discordance during treatment with protease inhibitor-based highly active antiretroviral therapy: immune response and viral control.

Mechanisms that underly discordant CD4+ cell/virus load (VL) responses in patients who receive highly active antiretroviral therapy (HAART) were studied in 30 human immunodeficiency virus (HIV)-positive patients, in 3 groups. Discordant responders maintained CD4+ cell levels >200/mm(3) with stable or increasing trend, despite sustained VLs of 500-5000 copies/mL, for >2 years. Treatment-success patients had CD4+ cell counts >200/mm(3) with stable or increasing trend and VLs <50 copies/mL, for >2 years. Treatment-failure patients initially responded to HAART, followed by decreasing CD4+ cell counts and increasing VLs. Interferon-gamma production to gag and noncytolytic CD8+ cell suppressive activity were greater in discordant responders. Cellular activation was greatest in patients with treatment failure. All discordant responders had non-syncytium-inducing (CCR5-tropic) viruses. Viruses from discordant responders and from patients with treatment failure had extensive resistance mutations; discordant responders had significantly lower viral replication capacities. These findings suggest that discordant responses may be related to enhanced HIV-directed immune responses, diminished cellular activation, decreased viral replication capacity, and preservation of non-syncytium-inducing virus strains.

Authors
Sufka, SA; Ferrari, G; Gryszowka, VE; Wrin, T; Fiscus, SA; Tomaras, GD; Staats, HF; Patel, DD; Sempowski, GD; Hellmann, NS; Weinhold, KJ; Hicks, CB
MLA Citation
Sufka, SA, Ferrari, G, Gryszowka, VE, Wrin, T, Fiscus, SA, Tomaras, GD, Staats, HF, Patel, DD, Sempowski, GD, Hellmann, NS, Weinhold, KJ, and Hicks, CB. "Prolonged CD4+ cell/virus load discordance during treatment with protease inhibitor-based highly active antiretroviral therapy: immune response and viral control." J Infect Dis 187.7 (April 1, 2003): 1027-1037.
PMID
12660916
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
187
Issue
7
Publish Date
2003
Start Page
1027
End Page
1037
DOI
10.1086/368359

Safety and immunogenicity of a high-titered canarypox vaccine in combination with rgp120 in a diverse population of HIV-1-uninfected adults: AIDS Vaccine Evaluation Group Protocol 022A.

To test the safety and immunogenicity of a high-titered preparation of ALVAC-HIV vCP205 in both high-risk and low-risk persons and to evaluate variations in dosing schedule, we conducted a multicenter, randomized, double-blind trial of this vector in combination with recombinant subunit gp120 in 150 HIV-1-seronegative volunteers. The high-titered ALVAC vaccine was well tolerated; adverse events were minimal and not influenced by dosing. At day 728, the cumulative probability of a cytotoxic T-lymphocyte (CTL) response was 76% (95% confidence interval [CI]: 64%-89%) among volunteers receiving vaccine, and the net amount attributable to vaccination was 50% (CI: 16%; 74%). The net probability of a repeated positive CTL response by day 728 was 50% (CI: 21%; 64%). There was a significant difference in CTL response at day 182 between volunteers who had received four doses versus three doses of vCP205 (42% vs. 24%, p =.052). The CTL response was similar in high-risk volunteers and vaccinia-naive volunteers compared with vaccinia-immune volunteers. Neutralizing antibody responses were detected in 95% of vaccinees at day 287, with higher geometric mean titers in recipients of sequential versus simultaneous dosing of the two vaccines and in vaccinia-naive volunteers. This high-titered preparation of ALVAC-HIV vCP205 in combination with gp120 was safe and immunogenic in a diverse group of HIV-1-seronegative volunteers.

Authors
Gupta, K; Hudgens, M; Corey, L; McElrath, MJ; Weinhold, K; Montefiori, DC; Gorse, GJ; Frey, SE; Keefer, MC; Evans, TG; Dolin, R; Schwartz, DH; Harro, C; Graham, B; Spearman, PW; Mulligan, M; Goepfert, P; AIDS Vaccine Evaluation Group,
MLA Citation
Gupta, K, Hudgens, M, Corey, L, McElrath, MJ, Weinhold, K, Montefiori, DC, Gorse, GJ, Frey, SE, Keefer, MC, Evans, TG, Dolin, R, Schwartz, DH, Harro, C, Graham, B, Spearman, PW, Mulligan, M, Goepfert, P, and AIDS Vaccine Evaluation Group, . "Safety and immunogenicity of a high-titered canarypox vaccine in combination with rgp120 in a diverse population of HIV-1-uninfected adults: AIDS Vaccine Evaluation Group Protocol 022A." J Acquir Immune Defic Syndr 29.3 (March 1, 2002): 254-261.
PMID
11873074
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
29
Issue
3
Publish Date
2002
Start Page
254
End Page
261

Thymopoiesis in HIV-infected adults after highly active antiretroviral therapy.

The thymus of HIV-seropositive patients can enlarge as CD4+ T cell counts increase on highly active anti-retroviral therapy (HAART). This may indicate development of new T cells or represent mature peripheral T cells recirculating to the thymus. To define the etiology of the enlargement, the thymuses of two HIV-infected individuals on HAART were biopsied. For more than 3 years before initiation of HAART, both patients (38 and 41 years of age) had documented CD4+ T lymphopenia. Peripheral blood samples were obtained to assess circulating CD4+ CD45RA+ CD62L+ T cells, which were thought to have recently developed in the thymus. Peripheral blood T cells from both patients and thymocytes from the second patient were also tested for levels of DNA episomes formed during T cell receptor gene rearrangement (T cell receptor rearrangement excision circles, TRECs). With HAART, peripheral blood CD4+ T cell counts increased from approximately 60/mm(3) to 552/mm(3) and 750/mm(3) for patients 1 and 2, respectively. Thymic biopsies from both patients showed normal thymus histology with active thymopoiesis. Percentages of peripheral blood CD4+ CD45RA+ CD62L+ T cells and quantitation of T cell TRECs also reflected active thymopoiesis in both patients. Thus, in these two HIV-seropositive adults examined after initiation of HAART, thymic enlargement represented active thymopoiesis. Thymopoiesis in adult AIDS patients may contribute to immune reconstitution even after prolonged CD4+ T lymphopenia.

Authors
Markert, ML; Alvarez-McLeod, AP; Sempowski, GD; Hale, LP; Horvatinovich, JM; Weinhold, KJ; Bartlett, JA; D'Amico, TA; Haynes, BF
MLA Citation
Markert, ML, Alvarez-McLeod, AP, Sempowski, GD, Hale, LP, Horvatinovich, JM, Weinhold, KJ, Bartlett, JA, D'Amico, TA, and Haynes, BF. "Thymopoiesis in HIV-infected adults after highly active antiretroviral therapy." AIDS Res Hum Retroviruses 17.17 (November 20, 2001): 1635-1643.
PMID
11779351
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
17
Issue
17
Publish Date
2001
Start Page
1635
End Page
1643
DOI
10.1089/088922201753342040

CD8 CTL responses in vaccines: emerging patterns of HLA restriction and epitope recognition.

We evaluated MHC-class I-restricted CTL responses induced by HIV-1 clade B-based vaccines in nine HIV-1 seronegative vaccine recipients with regard to their patterns of HLA restriction and epitope recognition. We found that seven of nine volunteers developed detectable CTL reactivities against novel epitopes within the HIV-1 Env and Gag proteins. Although four of nine subjects were HLA-A*0201, none of the cellular responses was restricted in the context of this allele. The type of responses observed in this sampling of vaccines appeared similar to those reported during primary infection and among long term non-progressors, with three out of nine subjects recognizing HLA-B27 or HLA-B17(57)-restricted epitopes. Although the majority of CTL responses were directed against novel epitopes, these effectors were still able to mediate cross-clade reactivities.

Authors
Ferrari, G; Neal, W; Jones, A; Olender, N; Ottinger, J; Ha, R; McElrath, MJ; Goepfert, P; Weinhold, KJ
MLA Citation
Ferrari, G, Neal, W, Jones, A, Olender, N, Ottinger, J, Ha, R, McElrath, MJ, Goepfert, P, and Weinhold, KJ. "CD8 CTL responses in vaccines: emerging patterns of HLA restriction and epitope recognition." Immunol Lett 79.1-2 (November 1, 2001): 37-45.
PMID
11595288
Source
pubmed
Published In
Immunology Letters
Volume
79
Issue
1-2
Publish Date
2001
Start Page
37
End Page
45

Immune reconstitution in human immunodeficiency virus-infected children receiving highly active antiretroviral therapy: a cohort study.

BACKGROUND: Highly active antiretroviral therapy (HAART) has brought about rapid declines in HIV-1 RNA concentrations and an increase in CD4+ counts in HIV-1-infected children. These changes are often accompanied by clinical improvement; however, the extent to which immune reconstitution occurs is not known. DESIGN: We compared two cohorts (n = 35) of HIV-1-infected children to evaluate the effects of HAART on immune recovery. Cohort 1 (C1) included clinically well children receiving HAART with a CD4 >22% at study initiation. Before HAART all children had moderately to severely suppressed immune function by CDC criteria (CD4 <25%) or CDC Category B or C disease. Cohort 2 (C2) included children with no current or past evidence of immunosuppression based on CDC criteria (CD4 >25%) and no evidence of clinical disease. Children in C2 were receiving a non-HAART regimen. METHODS: Immunophenotyping was performed to characterize CD4+ and CD8+ subsets with regard to maturation and activation. T cell rearrangement excision circles (TRECs) were measured to quantify recent thymic emigrants. RESULTS: No difference was found in percent CD4+ or percent CD8+ T cells or maturation markers between C1 and C2. There was significantly less expression of activation markers in both CD4+ and CD8+ cells in C1. There was no difference in TREC production between C1 and C2. CONCLUSION: Moderately to severely suppressed HIV-1-infected children receiving HAART are able to reconstitute their immune systems to a degree that is indistinguishable from that of stable, CDC Class A1 HIV-1-infected children with regard to CD4+ and CD8+ T cell subsets, expression of cellular maturation markers and TREC production.

Authors
Johnston, AM; Valentine, ME; Ottinger, J; Baydo, R; Gryszowka, V; Vavro, C; Weinhold, K; St Clair, M; McKinney, RE
MLA Citation
Johnston, AM, Valentine, ME, Ottinger, J, Baydo, R, Gryszowka, V, Vavro, C, Weinhold, K, St Clair, M, and McKinney, RE. "Immune reconstitution in human immunodeficiency virus-infected children receiving highly active antiretroviral therapy: a cohort study." Pediatr Infect Dis J 20.10 (October 2001): 941-946.
PMID
11642627
Source
pubmed
Published In
Pediatric Infectious Disease Journal
Volume
20
Issue
10
Publish Date
2001
Start Page
941
End Page
946

Immunologic and virologic analyses of an acutely HIV type 1-infected patient with extremely rapid disease progression.

The immunologic and virologic factors that impact on the rate of disease progression after acute infection with human immunodeficiency virus (HIV) type 1 are poorly understood. A patient with an extraordinarily rapid disease course leading to AIDS-associated death within 6 months of infection was studied intensively for the presence of anti-HIV immune reactivities as well as changes in the genetic and biologic properties of virus isolates. Although altered humoral responses were evident, the most distinctive immunologic feature was a nearly complete absence of detectable HIV-specific CTL responses. In addition to a rapid decline in CD3+CD4+ cells, elevated percentages of CD8+CD45RA+ and CD8+CD57+ cells and diminished CD8+CD45R0+ and CD8+CD28+ cells were evident. Primary viral isolates recovered throughout the course of infection exhibited limited sequence diversity. Cloned viral envelopes were found to have unusually broad patterns of coreceptor usage for cell-cell fusion, although infectivity studies yielded no evidence of infection via these alternative receptors. The infectivity studies demonstrated that these isolates and their envelopes maintained an R5 phenotype throughout the course of disease. The absence of demonstrable anti-HIV CTL reactivities, coupled with a protracted course of seroconversion, highlights the importance of robust HIV-specific immune responses in the control of disease progression.

Authors
Demarest, JF; Jack, N; Cleghorn, FR; Greenberg, ML; Hoffman, TL; Ottinger, JS; Fantry, L; Edwards, J; O'Brien, TR; Cao, K; Mahabir, B; Blattner, WA; Bartholomew, C; Weinhold, KJ
MLA Citation
Demarest, JF, Jack, N, Cleghorn, FR, Greenberg, ML, Hoffman, TL, Ottinger, JS, Fantry, L, Edwards, J, O'Brien, TR, Cao, K, Mahabir, B, Blattner, WA, Bartholomew, C, and Weinhold, KJ. "Immunologic and virologic analyses of an acutely HIV type 1-infected patient with extremely rapid disease progression." AIDS Res Hum Retroviruses 17.14 (September 20, 2001): 1333-1344.
PMID
11602044
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
17
Issue
14
Publish Date
2001
Start Page
1333
End Page
1344
DOI
10.1089/08892220152596597

Immunologic profile of human immunodeficiency virus-infected patients during viral remission and relapse on antiretroviral therapy.

A dissociation between plasma human immunodeficiency virus (HIV) RNA levels and CD4(+) cell counts has been reported in patients experiencing viral relapse while receiving antiretroviral therapy. This study compared patients with stable CD4(+) lymphocytes during viral relapse while receiving treatment with patients who had sustained virus suppression. Plasma HIV RNA levels, lymphocyte immunophenotyping, and T cell receptor excision circle (TREC) levels were measured. Naive CD4(+) lymphocyte phenotype and TREC levels were not significantly different in patients with virus suppression or in those who had relapsed. However, CD8(+) lymphocyte activation, including the number and percentage of activated cells and CD38 antibody-binding capacity, was significantly elevated during viral relapse, compared with that in suppressed patients. By multivariable regression analyses, CD8(+) and CD4(+) lymphocyte activation were associated significantly with increasing plasma HIV RNA levels.

Authors
Wellons, MF; Ottinger, JS; Weinhold, KJ; Gryszowka, V; Sanders, LL; Edwards, LJ; Gooding, ME; Thomasch, JR; Bartlett, JA
MLA Citation
Wellons, MF, Ottinger, JS, Weinhold, KJ, Gryszowka, V, Sanders, LL, Edwards, LJ, Gooding, ME, Thomasch, JR, and Bartlett, JA. "Immunologic profile of human immunodeficiency virus-infected patients during viral remission and relapse on antiretroviral therapy." J Infect Dis 183.10 (May 15, 2001): 1522-1525.
PMID
11319689
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
183
Issue
10
Publish Date
2001
Start Page
1522
End Page
1525
DOI
10.1086/320193

QS-21 promotes an adjuvant effect allowing for reduced antigen dose during HIV-1 envelope subunit immmunization in humans

Three separate studies were undertaken in HIV-1 uninfected persons to determine if the adjuvant QS-21 improves the magnitude or kinetics of immune responses induced by recombinant soluble gp120 HIV-1MN protein (rsgp120) immunization. The QS-21 was administered at two doses (50 and 100 μg), either alone or in combination with aluminum hydroxide (600 μg). At the highest doses of rsgp120 (100, 300, and 600 μg), QS-21 exerted no significant effect on either binding or neutralizing antibody titers. Antibody binding and neutralizing responses fell dramatically when rsgp120, formulated with alum alone, was given at low doses (3 and 30 μg). In contrast, antibody responses similar in titer to those in the high dose antigen groups were induced with the low dose rsgp120 formulated with QS-21. In addition, the lymphocyte proliferation and delayed type hypersensitivity skin testing were superior in the QS-21 recipients compared with the alum recipients at the low antigen doses. Moderate to severe pain was observed in majority of the volunteers receiving QS-21 formulations, and vasovagal episodes and hypertension were not infrequent. Thus, the use of QS-21 may provide a means to reduce the dose of a soluble protein immunogen. © 2001 Elsevier Science Ltd.

Authors
Evans, TG; McElrath, MJ; Matthews, T; Montefiori, D; Weinhold, K; Wolff, M; Keefer, MC; Kallas, EG; Corey, L; Gorse, GJ; Belshe, R; Graham, BS; Spearman, PW; Schwartz, D; Mulligan, MJ; Goepfert, P; Fast, P; Berman, P; Powell, M; Francis, D
MLA Citation
Evans, TG, McElrath, MJ, Matthews, T, Montefiori, D, Weinhold, K, Wolff, M, Keefer, MC, Kallas, EG, Corey, L, Gorse, GJ, Belshe, R, Graham, BS, Spearman, PW, Schwartz, D, Mulligan, MJ, Goepfert, P, Fast, P, Berman, P, Powell, M, and Francis, D. "QS-21 promotes an adjuvant effect allowing for reduced antigen dose during HIV-1 envelope subunit immmunization in humans." Vaccine 19.15-16 (2001): 2080-2091.
PMID
11228380
Source
scival
Published In
Vaccine
Volume
19
Issue
15-16
Publish Date
2001
Start Page
2080
End Page
2091
DOI
10.1016/S0264-410X(00)00415-1

Cellular and humoral immune responses to a canarypox vaccine containing human immunodeficiency virus type 1 env, gag, and pro in combination with RGP120

Elicitation of both memory cytotoxic T cell responses and human immunodeficiency virus (HIV)-neutralizing antibodies are desirable characteristics of an HIV vaccine regimen. We studied a combination vaccine regimen consisting of a canarypox (CP) vector containing env, gag, and pro, in combination with a recombinant gp120 subunit protein. Twenty-six of 42 subjects who received CP vac-env-pro demonstrated in vitro CD8+ T cell responses, versus 3 of 17 who received the control CP rabies or gp120 vaccine only (P = .0003); 15 of these 26 demonstrated a CD8+ cytotoxic T lymphocyte (CTL) response on ≥2 occasions postvaccination. The frequency of CD8+ CTL response to HIV antigens was similar between vaccinianaive and vaccinia-immune persons. Rgp120 immunization did not increase the CD8+ CTL response to HIV type 1 envelope proteins, but rgp120 boosting did markedly enhanced the titer and frequency of neutralizing antibodies to the MN strain of HIV. Overall, the combination of a CP gag, pro, env vector, in combination with recombinant gp120, resulted in neutralizing antibodies in 91% of subjects and CD8+ T cell responses in 62% of subjects. A nonreplicating pox virus shuttle vector vaccine appears to be capable of eliciting CD8+ CTL responses in most healthy volunteers, whether they were vaccinia naive or vaccinia immune.

Authors
Corey, L; Mulligan, M; Goepfert, P; Sabbaj, S; Clements-Mann, ML; Harrow, C; Schwartz, D; Dolin, R; Evans, T; Keefer, M; Belshe, R; Gorse, G; Frey, S; McElrath, J; Graham, B; Wright, P; Spearman, P; Weinhold, K; Montefiori, D; Greenberg, M; Klein, M; Habib, RE; Excler, JL; Duliege, A-M; Stablein, D; Wolff, M; Smith, C; Grabowsky, M; Savarese, B; Walker, MC
MLA Citation
Corey, L, Mulligan, M, Goepfert, P, Sabbaj, S, Clements-Mann, ML, Harrow, C, Schwartz, D, Dolin, R, Evans, T, Keefer, M, Belshe, R, Gorse, G, Frey, S, McElrath, J, Graham, B, Wright, P, Spearman, P, Weinhold, K, Montefiori, D, Greenberg, M, Klein, M, Habib, RE, Excler, JL, Duliege, A-M, Stablein, D, Wolff, M, Smith, C, Grabowsky, M, Savarese, B, and Walker, MC. "Cellular and humoral immune responses to a canarypox vaccine containing human immunodeficiency virus type 1 env, gag, and pro in combination with RGP120." Journal of Infectious Diseases 183.4 (2001): 563-570.
PMID
11170981
Source
scival
Published In
Journal of Infectious Diseases
Volume
183
Issue
4
Publish Date
2001
Start Page
563
End Page
570
DOI
10.1086/318523

Safety and immunogenicity of a canarypox-vectored human immunodeficiency virus type 1 vaccine with or without gp120: A phase 2 study in higher- and lower-risk volunteers

Live attenuated viral vectors that express human immunodeficiency virus (HIV) antigens are being developed as potential vaccines to prevent HIV infection. The first phase 2 trial with a canarypox vector (vCP205, which expresses gp120, p55, and protease) was conducted in 435 volunteers with and without gp120 boosting, to expand the safety database and to compare the immunogenicity of the vector in volunteers who were at higher risk with that in volunteers at lower risk for HIV infection. Neutralizing antibodies to the MN strain were stimulated in 94% of volunteers given vCP205 plus gp120 and in 56% of volunteers given vCP205 alone. CD8+ cytotoxic T lymphocyte cells developed at some time point in 33% of volunteers given vCP205, with or without gp120. Phase 3 field trials with these or similar vaccines are needed, to determine whether efficacy in preventing HIV infection or in slowing disease progression among vaccinees who become infected is associated with the level and types of immune responses that were induced by the vaccines in this study.

Authors
Belshe, RB; Stevens, C; Gorse, GJ; Buchbinder, S; Weinhold, K; Sheppard, H; Stablein, D; Self, S; McNamara, J; Frey, S; Flores, J; Excler, JL; Klein, M; Habib, RE; Duliege, A-M; Harro, C; Corey, L; Keefer, M; Mulligan, M; Wright, P; Celum, C; Judson, F; Mayer, K; McKirnan, D; Marmor, M; Woody, G
MLA Citation
Belshe, RB, Stevens, C, Gorse, GJ, Buchbinder, S, Weinhold, K, Sheppard, H, Stablein, D, Self, S, McNamara, J, Frey, S, Flores, J, Excler, JL, Klein, M, Habib, RE, Duliege, A-M, Harro, C, Corey, L, Keefer, M, Mulligan, M, Wright, P, Celum, C, Judson, F, Mayer, K, McKirnan, D, Marmor, M, and Woody, G. "Safety and immunogenicity of a canarypox-vectored human immunodeficiency virus type 1 vaccine with or without gp120: A phase 2 study in higher- and lower-risk volunteers." Journal of Infectious Diseases 183.9 (2001): 1343-1352.
PMID
11294665
Source
scival
Published In
Journal of Infectious Diseases
Volume
183
Issue
9
Publish Date
2001
Start Page
1343
End Page
1352
DOI
10.1086/319863

A Phase I safety and immunogenicity trial of UBI® microparticulate monovalent HIV-1 MN oral peptide immunogen with parenteral boost in HIV-1 seronegative human subjects

Thirty-three HIV-seronegative adults were recruited into a Phase I safety and immunogenicity HIV-1 vaccine trial. The immunogens were as follows: a synthetic, monovalent, octameric HIV-1 MN V3 peptide in aluminum hydroxide (alum) adjuvant administered by intramuscular delivery; and a similar product encapsulated in biodegradable micro-spheres composed of co-polymers of lactic and glycolic acids, administered by the oral route. These were administered in three sequential oral doses, followed by a parenteral boost. No serious adverse experiences were observed. Oral administration of this vaccine, alone or in combination with parenteral boosting, resulted in no significant humoral, cellular, or mucosal immune responses. © 2001 Elsevier Science Ltd.

Authors
Lambert, JS; Keefer, M; Mulligan, MJ; Schwartz, D; Mestecky, J; Weinhold, K; Smith, C; Hsieh, R; Moldoveanu, Z; Fast, P; Forrest, B; Koff, W
MLA Citation
Lambert, JS, Keefer, M, Mulligan, MJ, Schwartz, D, Mestecky, J, Weinhold, K, Smith, C, Hsieh, R, Moldoveanu, Z, Fast, P, Forrest, B, and Koff, W. "A Phase I safety and immunogenicity trial of UBI® microparticulate monovalent HIV-1 MN oral peptide immunogen with parenteral boost in HIV-1 seronegative human subjects." Vaccine 19.23-24 (2001): 3033-3042.
PMID
11311997
Source
scival
Published In
Vaccine
Volume
19
Issue
23-24
Publish Date
2001
Start Page
3033
End Page
3042
DOI
10.1016/S0264-410X(01)00051-2

Polymorphisms in HLA class I genes associated with both favorable prognosis of human immunodeficiency virus (HIV) type 1 infection and positive cytotoxic T-lymphocyte responses to ALVAC-HIV recombinant canarypox vaccines

Carriers of certain human leukocyte antigen class I alleles show favorable prognosis of human immunodeficiency virus type 1 (HIV-1) infection, presumably due to effective CD8+ cytotoxic T-lymphocyte responses, but close relationships between class I variants mediating such responses to natural and to vaccine HIV-1 antigen have not been established. During 6 to 30 months of administration and follow-up in trials of ALVAC-HIV recombinant canarypox vaccines, cells from 42% of 291 HIV-1-negative vaccinated subjects typed at class I loci responded to an HIV-1 protein in a lytic bulk CD8+ cytotoxic T-lymphocyte assay. By 2 weeks after the second dose, higher proportions of vaccinees carrying one of two alleles consistently associated with slower progression of natural HIV-1 infection reacted at least once: B*27 carriers reacted to Gag (64%; odds ratio [OR] = 10.3, P = 0.001) and Env (36%; OR = 4.6, P = 0.04), and B*57 carriers reacted to Env (44%; OR = 6.6, P < 0.05). By 2 weeks after the third or fourth dose, B*27 carriers had responded (two or more reactions) to Gag (33%; OR = 4.4, P < 0.05) and B*57 carriers had responded to both Gag (39%; OR = 5.3, P = 0.013) and Env (39%; OR = 9.5, P = 0.002). Homozygosity at class I loci, although conferring an unfavorable prognosis following natural infection, showed no such disadvantage for vaccine response. Individual class I alleles have not previously demonstrated such clear and consistent relationship with both the clinical course of an infection and cellular immunity to a vaccine against the infectious agent. This proof of principle that class I an alleles modulate both processes has implications for development of HIV-1 and presumably other vaccines.

Authors
Kaslow, RA; Rivers, C; Tang, J; Bender, TJ; Goepfert, PA; Habib, RE; Weinhold, K; Mulligan, MJ; Clements-Mann, ML; Schwartz, D; Belshe, R; Gorse, G; Frey, S; Dolin, R; Keefer, M; Evans, T; Corey, L; McElrath, J; Graham, B; Wright, P; Spearman, P
MLA Citation
Kaslow, RA, Rivers, C, Tang, J, Bender, TJ, Goepfert, PA, Habib, RE, Weinhold, K, Mulligan, MJ, Clements-Mann, ML, Schwartz, D, Belshe, R, Gorse, G, Frey, S, Dolin, R, Keefer, M, Evans, T, Corey, L, McElrath, J, Graham, B, Wright, P, and Spearman, P. "Polymorphisms in HLA class I genes associated with both favorable prognosis of human immunodeficiency virus (HIV) type 1 infection and positive cytotoxic T-lymphocyte responses to ALVAC-HIV recombinant canarypox vaccines." Journal of Virology 75.18 (2001): 8681-8689.
PMID
11507213
Source
scival
Published In
Journal of Virology
Volume
75
Issue
18
Publish Date
2001
Start Page
8681
End Page
8689
DOI
10.1128/JVI.75.18.8681-8689.2001

V beta repertoire of T lymphocytes emerging in adults after unrelated umbilical cord blood (UCB) allogeneic transplantation.

Authors
Demarest, JF; Kadereit, S; Brenner-Jones, S; Langdon, S; Kelly, MA; Mathieson, J; Miller, R; Mohammed, S; Mandel, D; McKinnon, K; Weinhold, KJ; Laughlin, MJ
MLA Citation
Demarest, JF, Kadereit, S, Brenner-Jones, S, Langdon, S, Kelly, MA, Mathieson, J, Miller, R, Mohammed, S, Mandel, D, McKinnon, K, Weinhold, KJ, and Laughlin, MJ. "V beta repertoire of T lymphocytes emerging in adults after unrelated umbilical cord blood (UCB) allogeneic transplantation." November 16, 2000.
Source
wos-lite
Published In
Blood
Volume
96
Issue
11
Publish Date
2000
Start Page
788A
End Page
788A

Identification of highly conserved and broadly cross-reactive HIV type 1 cytotoxic T lymphocyte epitopes as candidate immunogens for inclusion in Mycobacterium bovis BCG-vectored HIV vaccines.

One of the fundamental goals of current strategies to develop an efficacious vaccine for AIDS is the elicitation of cytotoxic T lymphocyte (CTL) reactivities capable of recognizing cells infected with different subtypes of the human immunodeficiency virus type 1 (HIV-1). In efforts to explore new vaccine candidates by the UNAIDS/WHO Vaccine Committee, we review the most recent data concerning CTL epitopes that are conserved among the different HIV-1 subtypes. Moreover, we examine HLA allelic frequencies in several different populations, to determine those that could contribute to the goal of a cumulative phenotype frequency (CP) of at least 80%. By analyzing conserved epitopes in the context of HLA restricting alleles, we define a set of HIV-1 gene regions that may have the greatest potential to induce cross-clade reactive CTLs. The absence of well-defined correlates of immune protection that link CTL epitopes to delayed disease progression and/or prevention of infection does not permit an assignment of rank order of the most relevant component of a candidate vaccine. Thus far, most of the studies conducted in clade B-infected patients to define conserved and immunodominant epitopes indicate gag and pol gene products to be the most conserved among the HIV-1 subtypes. Moreover, anti-Pol and -Gag CTL responses appear to correlate inversely with disease progression, suggesting that they should be among the first choice of antigens to be included in a candidate vaccine construct aimed at induction of broad CTL responses. The impact of a clade B-based vaccine as a worldwide candidate capable of inducing protective immune responses can be determined only after "in vivo" studies. Meanwhile, extensive parallel studies in populations infected with non-clade B HIV-1 subtypes should define the patterns of immunodominant epitopes and HLA for comparison with the data already collected in clade B-infected subjects.

Authors
Ferrari, G; Kostyu, DD; Cox, J; Dawson, DV; Flores, J; Weinhold, KJ; Osmanov, S
MLA Citation
Ferrari, G, Kostyu, DD, Cox, J, Dawson, DV, Flores, J, Weinhold, KJ, and Osmanov, S. "Identification of highly conserved and broadly cross-reactive HIV type 1 cytotoxic T lymphocyte epitopes as candidate immunogens for inclusion in Mycobacterium bovis BCG-vectored HIV vaccines." AIDS Res Hum Retroviruses 16.14 (September 20, 2000): 1433-1443. (Review)
PMID
11018863
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
16
Issue
14
Publish Date
2000
Start Page
1433
End Page
1443
DOI
10.1089/08892220050140982

A distinctive clade B HIV type 1 is heterosexually transmitted in Trinidad and Tobago.

HIV-1 transmission worldwide is predominantly associated with heterosexual activity, and non-clade B viruses account for the most spread. The HIV-1 epidemic in Trinidad/Tobago and the Caribbean shares many features with such heterosexual epidemics, including a prominent role for coincident sexually transmitted diseases. This study evaluates the molecular epidemiology of HIV-1 in Trinidad/Tobago during a period when abrupt transition from homosexual to heterosexual transmission occurred in the absence of injecting drug use, concomitant with a rapid rise in HIV-1 prevalence in the heterosexual population. Of 31 viral isolates studied during 1987-1995, all cluster with subtype B reference strains. In the analysis of full env genes from 22 early seroconverters, the Trinidad isolates constitute a significant subcluster within the B subtype. The Trinidad V3 consensus sequence differs by a single amino acid from the prototype B V3 consensus and demonstrates stability over the decade of this study. In the majority of isolates, the V3 loop of env contains a signature threonine deletion that marks the lineage of the Trinidad HIV-1 clade B epidemic from pre-1984. No phenotypic features, including syncitium induction, neutralization profiles, and chemokine receptor usage, distinguish this virus population from other subtype B viruses. Thus, although the subtype B HIV-1 viruses being transmitted in Trinidad are genetically distinguishable from other subtype B viruses, this is probably the result of a strong founder effect in a geographically circumscribed population rather than genetic selection for heterosexual transmission. These results demonstrate that canonical clade B HIV-1 can generate a typical heterosexual epidemic.

Authors
Cleghorn, FR; Jack, N; Carr, JK; Edwards, J; Mahabir, B; Sill, A; McDanal, CB; Connolly, SM; Goodman, D; Bennetts, RQ; O'Brien, TR; Weinhold, KJ; Bartholomew, C; Blattner, WA; Greenberg, ML
MLA Citation
Cleghorn, FR, Jack, N, Carr, JK, Edwards, J, Mahabir, B, Sill, A, McDanal, CB, Connolly, SM, Goodman, D, Bennetts, RQ, O'Brien, TR, Weinhold, KJ, Bartholomew, C, Blattner, WA, and Greenberg, ML. "A distinctive clade B HIV type 1 is heterosexually transmitted in Trinidad and Tobago." Proc Natl Acad Sci U S A 97.19 (September 12, 2000): 10532-10537.
PMID
10984542
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
97
Issue
19
Publish Date
2000
Start Page
10532
End Page
10537

CD8+ T cell-mediated suppressive activity inhibits HIV-1 after virus entry with kinetics indicating effects on virus gene expression.

Individuals infected with HIV-1 have varying rates of progression to AIDS. Cellular immune responses, comprised of cytolytic and noncytolytic CD8(+) T cell effector functions, are considered important for controlling viremia and maintaining the clinically asymptomatic state. Although there is general agreement regarding CD8(+) T lymphocyte cytotoxic functions, considerable controversy exists over the nature of the noncytolytic antiviral activity of CD8(+) cells. The discovery that RANTES (regulated on activation, normal T cell expressed and secreted), MIP-1alpha, and MIP-1beta (macrophage inflammatory protein 1 alpha and beta) could inhibit HIV-1 replication by blocking viral entry processes led to the notion that these molecules are responsible for the CD8(+) cell suppressive activity. However, T tropic HIV isolates requiring the CXCR4 coreceptor for entry are insensitive to the antiviral effects of these beta-chemokines. Using a CXCR4-dependent virus, we determined that the mechanism of CD8(+) T cell-mediated activity did act after viral entry into the host cell. We also define the kinetics of the HIV life cycle in primary activated human CD4(+)-enriched T cells by using an HIV-1 reporter virus system pseudotyped with the CXCR4-dependent HIV-1 envelope gene of NL4-3. Analysis of these kinetic data indicates that CD8(+) T cell-mediated suppressive activity acts at a stage in the viral life cycle after entry and independently of the HIV envelope. Additionally, we show that the antiviral activity targets stages of the virus life cycle correlating with transcription and early proviral gene expression. These findings not only provide a range of possible targets for the CD8(+) T cell-mediated activity but also support the notion that this antiviral activity is multifactorial in nature.

Authors
Tomaras, GD; Lacey, SF; McDanal, CB; Ferrari, G; Weinhold, KJ; Greenberg, ML
MLA Citation
Tomaras, GD, Lacey, SF, McDanal, CB, Ferrari, G, Weinhold, KJ, and Greenberg, ML. "CD8+ T cell-mediated suppressive activity inhibits HIV-1 after virus entry with kinetics indicating effects on virus gene expression." Proc Natl Acad Sci U S A 97.7 (March 28, 2000): 3503-3508.
PMID
10725407
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
97
Issue
7
Publish Date
2000
Start Page
3503
End Page
3508
DOI
10.1073/pnas.070521097

Effect of highly active antiretroviral therapy and thymic transplantation on immunoreconstitution in HIV infection.

The purpose of this study was to determine whether thymic transplantation in addition to highly active antiretroviral therapy (HAART) will restore T cell function in HIV infection. Eight treatment-naive HIV-infected patients with CD4+ T cell counts of 200-500/mm3 were randomized into thymic transplantation and control arms. All patients received HAART (zidovudine, lamivudine, and ritonavir) for 6 weeks prior to transplantation. Thymic transplantation was done without immunosuppression, using postnatal HLA-unmatched cultured allogeneic thymus tissue. Patients were immunized every 6 months with the neoantigen keyhole limpet hemocyanin (KLH) and the recall antigen tetanus toxoid (TT). T cell phenotype and function and T cell receptor rearrangement excision circles (TRECs) were assessed. Thymic allografts were biopsied at 2 months. Six HIV-infected patients completed the study. Four patients received cultured allogeneic postnatal thymic grafts, two others were controls. CD4+ T cell counts increased and T cell-proliferative responses to Candida antigen and TT normalized in all patients. Proliferative responses to KLH developed in three of four transplant recipients and one of two controls. Patients responding to KLH after secondary immunization had greater TREC increases compared with the patients who did not respond. All thymic allografts were rejected within 2 months. In summary, four of six patients developed T cell-proliferative responses to the neoantigen KLH over the first 2 years of HAART. The transplanted thymus tissue, however, was rejected. There was no clear difference in restoration of T cell function in the transplant recipients compared with the controls. Increases in TRECs after initiation of HAART may correlate with improved immune function.

Authors
Markert, ML; Hicks, CB; Bartlett, JA; Harmon, JL; Hale, LP; Greenberg, ML; Ferrari, G; Ottinger, J; Boeck, A; Kloster, AL; McLaughlin, TM; Bleich, KB; Ungerleider, RM; Lyerly, HK; Wilkinson, WE; Rousseau, FS; Heath-Chiozzi, ME; Leonard, JM; Haase, AT; Shaw, GM; Bucy, RP; Douek, DC; Koup, RA; Haynes, BF; Bolognesi, DP; Weinhold, KJ
MLA Citation
Markert, ML, Hicks, CB, Bartlett, JA, Harmon, JL, Hale, LP, Greenberg, ML, Ferrari, G, Ottinger, J, Boeck, A, Kloster, AL, McLaughlin, TM, Bleich, KB, Ungerleider, RM, Lyerly, HK, Wilkinson, WE, Rousseau, FS, Heath-Chiozzi, ME, Leonard, JM, Haase, AT, Shaw, GM, Bucy, RP, Douek, DC, Koup, RA, Haynes, BF, Bolognesi, DP, and Weinhold, KJ. "Effect of highly active antiretroviral therapy and thymic transplantation on immunoreconstitution in HIV infection." AIDS Res Hum Retroviruses 16.5 (March 20, 2000): 403-413.
PMID
10772526
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
16
Issue
5
Publish Date
2000
Start Page
403
End Page
413
DOI
10.1089/088922200309061

HIV vaccine development at Duke University Medical Center.

With the AIDS epidemic continuing to spread throughout the world, development of a safe, practical, and effective HIV vaccine is a national priority. HIV vaccine research efforts are currently targeted towards design of HIV immunogens that induce both cellular and humoral immunity. This brief review summarizes ongoing work at the Duke University School of Medicine on HIV vaccine development.

Authors
Haynes, BF; Liao, HX; Staats, HF; Alam, MS; Weinhold, KJ; Montefiori, DC
MLA Citation
Haynes, BF, Liao, HX, Staats, HF, Alam, MS, Weinhold, KJ, and Montefiori, DC. "HIV vaccine development at Duke University Medical Center." Immunol Res 22.2-3 (2000): 263-269. (Review)
PMID
11339361
Source
pubmed
Published In
Immunologic Research
Volume
22
Issue
2-3
Publish Date
2000
Start Page
263
End Page
269

Cytokine profiles in seronegative volunteers immunized with a recombinant canarypox and gp120 prime-boost HIV-1 vaccine

Objectives: To study memory T cell proliferative responses and cytokine profiles induced in HIV-1 seronegative volunteers immunized with a live recombinant canarypox vector expressing HIV-1 antigens (ALVAC-HIV) and boosted with a recombinant gp120 subunit vaccine. Design: HIV-specific T cell proliferative responses and cytokines were measured 2 weeks after vaccination. Cytokines secreted by T helper 1 cells (Th1) [interleukin (IL)-2 and interferon-γ (IFN-γ)] and T helper 2 (Th2) cells (IL-4, IL-5, IL-6, and IL-10) were assessed both at the mRNA and the protein level. Methods: Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with HIV antigens. Subsequently, T cell proliferation was measured in a standard lymphoproliferation assay; secreted cytokines were measured using an enzyme-linked immunosorbent assay and upregulation of cytokine mRNA was measured using reverse transcriptase polymerase chain reaction. Results: All individuals who had received ALVAC-HIV followed by the protein vaccine exhibited HIV-1-specific T cell proliferative responses. Moreover, the PBMC of all prime-boost vaccinated individuals produced detectable IFN-γ and IL-10 in response to stimulation with HIV-1 envelope glycoprotein antigens; 83% also had detectable levels of IL-2 and IL-6, 71% had detectable levels of IL-4, and 86% had detectable levels of IL-5. Conclusions: These data indicate that this vaccination regimen was inducing both Th1- and Th2-type responses to HIV-1 envelope antigens. This prime-boost vaccination approach elicited T cell help for the generation of cytotoxic T lymphocyte responses as well as help for antibody production and so promises to generate a broad HIV-1-specific immune response. (C) 2000 Lippincott Williams and Wilkins.

Authors
Sabbaj, S; Mulligan, MJ; Hsieh, R-H; Belshe, RB; McGhee, JR; Schwartz, D; Burke, D; Gorse, GJ; Frey, S; Mestecky, J; Jackson, S; Gnann, JW; Goepfert, PA; Dolin, R; Keefer, MC; Evans, TG; McElrath, MJ; Corey, L; Graham, BS; Wright, P; Spearman, P; Matthews, T; Montefiori, D; Weinhold, K; Bolognesi, D; Allen, M; Savarese, B
MLA Citation
Sabbaj, S, Mulligan, MJ, Hsieh, R-H, Belshe, RB, McGhee, JR, Schwartz, D, Burke, D, Gorse, GJ, Frey, S, Mestecky, J, Jackson, S, Gnann, JW, Goepfert, PA, Dolin, R, Keefer, MC, Evans, TG, McElrath, MJ, Corey, L, Graham, BS, Wright, P, Spearman, P, Matthews, T, Montefiori, D, Weinhold, K, Bolognesi, D, Allen, M, and Savarese, B. "Cytokine profiles in seronegative volunteers immunized with a recombinant canarypox and gp120 prime-boost HIV-1 vaccine." AIDS 14.10 (2000): 1365-1374.
PMID
10930151
Source
scival
Published In
AIDS
Volume
14
Issue
10
Publish Date
2000
Start Page
1365
End Page
1374
DOI
10.1097/00002030-200007070-00009

Resistance to human immunodeficiency virus type 1 in vitro as a surrogate of vaccine-induced protective immunity

An in vitro assay developed as a correlate of vaccine-induced protection from human immunodeficiency virus (HIV) was validated in populations with relative resistance to HIV-1 as well as in HIV vaccine recipients. Cultures of peripheral blood mononuclear cells (PBMC) were challenged with 10 TCID50 of HIV-1(MN) or HIV-1(BaL), titered in PBMC from normal controls (n = 57). PBMC from HIV-1-infected persons with low viremia (n = 17), exposed uninfected persons (n = 23), and HIV-2-infected Senegalese prostitutes (n = 9) were significantly resistant to HIV-1(BaL) and/or HIV-1(MN) (P < .001). Among 34 HIV vaccine recipients of live canarypox vector expressing multiple HIV-1 gene products with or without rgp120 booster, PBMC from postvaccination samples were significantly resistant to both strains (P < .001), and cytotoxic T lymphocyte precursor-positive samples were significantly more resistant than were precursor-negative samples (P < .03). This is the first evidence of the induction by vaccination of a validated correlate of protection. This assay should serve as a useful criterion for assessing experimental HIV vaccines before phase III efficacy trials.

Authors
Castillo, RC; Arango-Jaramillo, S; John, R; Weinhold, K; Kanki, P; Carruth, L; Schwartz, DH
MLA Citation
Castillo, RC, Arango-Jaramillo, S, John, R, Weinhold, K, Kanki, P, Carruth, L, and Schwartz, DH. "Resistance to human immunodeficiency virus type 1 in vitro as a surrogate of vaccine-induced protective immunity." Journal of Infectious Diseases 181.3 (2000): 897-903.
PMID
10720510
Source
scival
Published In
Journal of Infectious Diseases
Volume
181
Issue
3
Publish Date
2000
Start Page
897
End Page
903
DOI
10.1086/315300

Immune responses in asymptomatic HIV-1-infected patients after HIV-DNA immunization followed by highly active antiretroviral treatment.

Intensive chemotherapy is capable of reducing the viral load in HIV-1-infected individuals while infected cells are still present. A special property of DNA immunization is to induce both new CTL and Ab responses. We evaluated the possibility of inducing new immune responses in already infected individuals by means of DNA constructs encoding the nef, rev, or tat regulatory HIV-1 genes. Significant changes in viral loads and CD4+ counts were observed in four patients who started highly active antiretroviral treatment (HAART) during the immunization study. The DNA immunization induced Ag-specific T cell proliferation, which persisted up to 9 mo after the last DNA injection, and cytolytic activities but did not, by itself, reduce viral load. Increased levels of CTL precursor cells were induced in all nine DNA-immunized patients. The profile of IFN-gamma secretion observed when human PBMC were transfected with the nef, rev, and tat DNA resembled that found in the CTL activity (nef > tat > rev). Ab responses that occurred after immunizations were of a low magnitude. In accordance with the high IL-6 production induced by the nef DNA plasmid, IgG titers were highest in patients immunized with nef DNA. The initiation of HAART appears to contribute to the induction of new HIV-specific CTL responses, but by itself did not cause obvious re-induction of these activities.

Authors
Calarota, SA; Leandersson, AC; Bratt, G; Hinkula, J; Klinman, DM; Weinhold, KJ; Sandström, E; Wahren, B
MLA Citation
Calarota, SA, Leandersson, AC, Bratt, G, Hinkula, J, Klinman, DM, Weinhold, KJ, Sandström, E, and Wahren, B. "Immune responses in asymptomatic HIV-1-infected patients after HIV-DNA immunization followed by highly active antiretroviral treatment." J Immunol 163.4 (August 15, 1999): 2330-2338.
PMID
10438897
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
163
Issue
4
Publish Date
1999
Start Page
2330
End Page
2338

A canarypox vaccine expressing multiple human immunodeficiency virus type 1 genes given alone or with rgp120 elicits broad and durable CD8+ cytotoxic T lymphocyte responses in seronegative volunteers.

Induction of CD8+ cytotoxic T cells is considered one of the important correlates for the protective efficacy of candidate human immunodeficiency virus type 1 (HIV-1) vaccines. To induce CD8+ cytotoxic T lymphocytes (CTLs) along with neutralizing antibody and CD4+ T cell help, a live canarypox virus construct expressing gp120, transmembrane gp41, the gag and protease genes, and sequences containing CTL epitopes in nef and pol was given simultaneously with, or followed by, rgp120 SF2. CD8+ CTLs were detected in 61% of volunteers at some time during the trial. Three to 6 months after the last immunization, the gene-specific responses were gag, 26/81; env, 17/77; nef, 12/77; and pol, 3/16. Simultaneous immunization with the canarypox vector and the subunit, beginning with the initial immunization, resulted in earlier antibody responses. In summary, a strategy of immunization with a canarypox vector expressing multiple genes of HIV-1 given with gp120 results in durable CD8+ CTL responses to a broad range of epitopes.

Authors
Evans, TG; Keefer, MC; Weinhold, KJ; Wolff, M; Montefiori, D; Gorse, GJ; Graham, BS; McElrath, MJ; Clements-Mann, ML; Mulligan, MJ; Fast, P; Walker, MC; Excler, JL; Duliege, AM; Tartaglia, J
MLA Citation
Evans, TG, Keefer, MC, Weinhold, KJ, Wolff, M, Montefiori, D, Gorse, GJ, Graham, BS, McElrath, MJ, Clements-Mann, ML, Mulligan, MJ, Fast, P, Walker, MC, Excler, JL, Duliege, AM, and Tartaglia, J. "A canarypox vaccine expressing multiple human immunodeficiency virus type 1 genes given alone or with rgp120 elicits broad and durable CD8+ cytotoxic T lymphocyte responses in seronegative volunteers." J Infect Dis 180.2 (August 1999): 290-298.
PMID
10395842
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
180
Issue
2
Publish Date
1999
Start Page
290
End Page
298
DOI
10.1086/314895

Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection.

Authors
Haynes, BF; Hale, LP; Weinhold, KJ; Patel, DD; Liao, HX; Bressler, PB; Jones, DM; Demarest, JF; Gebhard-Mitchell, K; Haase, AT; Bartlett, JA
MLA Citation
Haynes, BF, Hale, LP, Weinhold, KJ, Patel, DD, Liao, HX, Bressler, PB, Jones, DM, Demarest, JF, Gebhard-Mitchell, K, Haase, AT, and Bartlett, JA. "Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection." J Clin Invest 103.6 (March 15, 1999): 921-.
PMID
10079114
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
103
Issue
6
Publish Date
1999
Start Page
921

V beta repertoire of T lymphocytes emerging after unrelated umbilical cord blood (UCB) transplantation.

Authors
Demarest, JF; Kurtzberg, J; Laughlin, MJ; Kadereit, S; Brenner-Jones, S; Iacobucci, M; McKinnon, K; Zakem-Cloud, H; Weinhold, KJ
MLA Citation
Demarest, JF, Kurtzberg, J, Laughlin, MJ, Kadereit, S, Brenner-Jones, S, Iacobucci, M, McKinnon, K, Zakem-Cloud, H, and Weinhold, KJ. "V beta repertoire of T lymphocytes emerging after unrelated umbilical cord blood (UCB) transplantation." March 12, 1999.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
13
Issue
4
Publish Date
1999
Start Page
A644
End Page
A644

Natural history of HIV-specific CTL activity during acute HIV infection: envelope CTL impact subsequent plasma viremia.

Authors
Demarest, JF; Jones, SB; Ferrari, G; Johnson, CJ; Greenberg, M; O'Brien, TO; Blattner, W; Edwards, J; Bartholomew, C; Cleghorn, F; Weinhold, KJ
MLA Citation
Demarest, JF, Jones, SB, Ferrari, G, Johnson, CJ, Greenberg, M, O'Brien, TO, Blattner, W, Edwards, J, Bartholomew, C, Cleghorn, F, and Weinhold, KJ. "Natural history of HIV-specific CTL activity during acute HIV infection: envelope CTL impact subsequent plasma viremia." March 12, 1999.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
13
Issue
4
Publish Date
1999
Start Page
A294
End Page
A294

Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection.

A key question in understanding the status of the immune system in HIV-1 infection is whether the adult thymus contributes to reconstitution of peripheral T lymphocytes. We analyzed the thymus in adult patients who died of HIV-1 infection. In addition, we studied the clinical course of HIV-1 infection in three patients thymectomized for myasthenia gravis and determined the effect of antiretroviral therapy on CD4(+) T cells. We found that five of seven patients had thymus tissue at autopsy and that all thymuses identified had inflammatory infiltrates surrounding lymphodepleted thymic epithelium. Two of seven patients also had areas of thymopoiesis; one of these patients had peripheral blood CD4(+) T-cell levels of <50/mm3 for 51 months prior to death. Of three thymectomized patients, one rapidly progressed to AIDS, one progressed to AIDS over seven years (normal progressor), whereas the third remains asymptomatic at least seven years after seroconversion. Both latter patients had rises in peripheral blood CD4(+) T cells after antiretroviral therapy. Most patients who died of complications of HIV-1 infection did not have functional thymus tissue, and when present, thymopoiesis did not prevent prolonged lymphopenia. Thymectomy before HIV-1 infection did not preclude either peripheral CD4(+) T-cell rises or clinical responses after antiretroviral therapy.

Authors
Haynes, BF; Hale, LP; Weinhold, KJ; Patel, DD; Liao, HX; Bressler, PB; Jones, DM; Demarest, JF; Gebhard-Mitchell, K; Haase, AT; Bartlett, JA
MLA Citation
Haynes, BF, Hale, LP, Weinhold, KJ, Patel, DD, Liao, HX, Bressler, PB, Jones, DM, Demarest, JF, Gebhard-Mitchell, K, Haase, AT, and Bartlett, JA. "Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection." J Clin Invest 103.4 (February 1999): 453-460.
PMID
10021452
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
103
Issue
4
Publish Date
1999
Start Page
453
End Page
460
DOI
10.1172/JCI5201

Erratum: Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection (The Journal of Clinical Investigation (1999) 103 (453- 460))

Authors
Haynes, BF; Hale, LP; Weinhold, KJ; Patel, DD; Liao, H-X; Bressler, PB; Jones, DM; Demarest, JF; Gebhard-Mitchell, K; Haase, AT; Bartlett, JA
MLA Citation
Haynes, BF, Hale, LP, Weinhold, KJ, Patel, DD, Liao, H-X, Bressler, PB, Jones, DM, Demarest, JF, Gebhard-Mitchell, K, Haase, AT, and Bartlett, JA. "Erratum: Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection (The Journal of Clinical Investigation (1999) 103 (453- 460))." Journal of Clinical Investigation 103.6 (1999): 921--.
Source
scival
Published In
Journal of Clinical Investigation
Volume
103
Issue
6
Publish Date
1999
Start Page
921-

Lack of infection in HIV-exposed individuals is associated with a strong CD8+ cell noncytotoxic anti-HIV response

Individuals repeatedly exposed to HIV, but who remain uninfected, form a population enriched for persons likely to have either natural or acquired resistance to the virus. We have studied four such exposed uninfected cohorts, representing 60 individuals, for evidence of protective immunity. This population included participants exposed to HIV through anal or vaginal receptive intercourse on multiple occasions over many years. We observed CD8+-cell noncytotoxic inhibition of HIV replication in acutely infected CD4+ cells in the vast majority of individuals most recently exposed to the virus (within 1 year). The levels of this CD8+-cell response were sufficient to inhibit the in vitro infection of the exposed subjects' peripheral blood mononuclear cells. We found no evidence of a significant role for CCR5 Δ32 mutation in this population, nor did CD4+ cell susceptibility to infection or HIV-specific cytotoxic T-lymphocytes correlate with resistance to infection in the individuals tested. Therefore, the observed strong noncytotoxic CD8+-cell anti-HIV responses may be an antiviral immune activity contributing to the apparent protection from infection in these exposed uninfected individuals.

Authors
Stranford, SA; Skurnick, J; Louria, D; Osmond, D; Chang, S-Y; Sninsky, J; Ferrari, G; Weinhold, K; Lindquist, C; Levy, JA
MLA Citation
Stranford, SA, Skurnick, J, Louria, D, Osmond, D, Chang, S-Y, Sninsky, J, Ferrari, G, Weinhold, K, Lindquist, C, and Levy, JA. "Lack of infection in HIV-exposed individuals is associated with a strong CD8+ cell noncytotoxic anti-HIV response." Proceedings of the National Academy of Sciences of the United States of America 96.3 (1999): 1030-1035.
PMID
9927688
Source
scival
Published In
Proceedings of the National Academy of Sciences of USA
Volume
96
Issue
3
Publish Date
1999
Start Page
1030
End Page
1035
DOI
10.1073/pnas.96.3.1030

Deficient antibody-dependent cellular cytotoxicity against human immunodeficiency virus (HIV)-expressing target cells in perinatal HIV infection

Peripheral blood mononuclear cells (PBMC) of human immunodeficiency virus (HIV)-infected children, age-matched HIV-seronegative controls, and HIV-infected asymptomatic and symptomatic adults were compared for their ability to mediate antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) cell-mediated cytotoxicity against target cells expressing HIV or herpes simplex virus (HSV) antigens. Target cells consisted of CD4 lymphocytes purified from PBMC of HIV-seronegative adults and incubated with the IIIB strain of HIV, HUT78 cells chronically infected with IIIB, and HSV-infected human fibroblasts. PBMC of asymptomatic HIV-infected adults were generally able to lyse CD4 cells expressing HIV antigens. Direct correlation was found between the magnitude of lysis and absolute CD4 cell counts in these individuals. In contrast to these results, PBMC from HIV- infected children were generally unable to lyse IIIB-expressing CD4 cells, regardless of the children's clinical status, age, or absolute CD4 cell counts. Cells from HIV-seronegative adults and children did not directly lyse these target cells either but, in contrast to cells of HIV-seropositive children, were able to mediate cell lysis when serum from an HIV-seropositive adult was added. However, effector cells from these HIV-infected children were able to mediate both ADCC against HSV-infected fibroblasts and NK cell- mediated cytotoxicity against IIIB-infected HUT78 cells. Reduced ability of PBMC from vertically HIV-infected children to mediate ADCC against HIV antigen-expressing CD4 cells may contribute to rapid progression to AIDS.

Authors
Ziegner, U; Campbell, D; Weinhold, K; Frank, I; Rutstein, R; Starr, SE
MLA Citation
Ziegner, U, Campbell, D, Weinhold, K, Frank, I, Rutstein, R, and Starr, SE. "Deficient antibody-dependent cellular cytotoxicity against human immunodeficiency virus (HIV)-expressing target cells in perinatal HIV infection." Clinical and Diagnostic Laboratory Immunology 6.5 (1999): 718-724.
PMID
10473524
Source
scival
Published In
Clinical and diagnostic laboratory immunology
Volume
6
Issue
5
Publish Date
1999
Start Page
718
End Page
724

HIV- 1(MN) recombinant glycoprotein 160 vaccine-induced cellular and humoral immunity boosted by HIV-1(MN) recombinant glycoprotein 120 vaccine

We evaluated prime-boost immunization with two recombinant envelope glycoprotein subunit vaccines (HIV-1(MN) recombinant gp160 vaccine in alum adjuvant [MN rgp160] and HIV-1(MN) recombinant gp120 vaccine in alum adjuvant [MN rgp120]) for safety and immunogenicity in healthy, HIV-1-uninfected adults. The rationale was to combine the helper T cell memory and binding antibody responses typically induced by rgp160 vaccines with the superior neutralizing antibody responses induced by rgp120 vaccines. In a double- blinded, controlled trial, volunteers were randomly assigned to receive MN rgp160 or adjuvant placebo, and a subset later received MN rgp120. The two vaccines were safe, but reactions to MN rgp160 and its adjuvant placebo exceeded those to MN rgp120. MN rgp160 induced IgG binding antibodies, including all IgG subclasses, to MN rgp160 in all vaccine recipients. HIV- 1(MN)-neutralizing and anti-V3 MN peptide-binding antibodies were observed in a majority of volunteers after the fourth MN rgp160 immunization, but at lower levels compared with immunization with MN rgp120 in historical controls. HIV-1-binding, neutralizing, and fusion inhibition antibodies were boosted to the highest levels among MN rgp160 recipients after MN rgp120 booster injections. MN rgp120 boosting appeared to alter the distribution of MN rgp160 vaccine-induced, anti-MN rgp160 IgG subclass antibodies. MN rgp160 induced helper T cell memory, measured by lymphocyte proliferation, Th1 and Th2 cytokine production, and skin testing. Strategies including both subunit vaccines may help maximize antibody and helper T cell memory responses to HIV-1 envelope glycoprotein.

Authors
Gorse, GJ; Corey, L; Patel, GB; Mandava, M; Hsieh, R-H; Matthews, TJ; Walker, MC; Mcelrath, MJ; Berman, PW; Eibl, MM; Belshe, RB; Schwartz, D; Harro, C; Clements-Mann, ML; Frey, SE; Kennedy, DJ; Mulligan, M; Goepfert, P; Mestecky, J; Jackson, S; Hook, E; Keefer, MC; Dolin, R; Graham, BS; Spearman, P; Wright, P; Weinhold, K; Bolognesi, D; Savarese, B; Grabowsky, M
MLA Citation
Gorse, GJ, Corey, L, Patel, GB, Mandava, M, Hsieh, R-H, Matthews, TJ, Walker, MC, Mcelrath, MJ, Berman, PW, Eibl, MM, Belshe, RB, Schwartz, D, Harro, C, Clements-Mann, ML, Frey, SE, Kennedy, DJ, Mulligan, M, Goepfert, P, Mestecky, J, Jackson, S, Hook, E, Keefer, MC, Dolin, R, Graham, BS, Spearman, P, Wright, P, Weinhold, K, Bolognesi, D, Savarese, B, and Grabowsky, M. "HIV- 1(MN) recombinant glycoprotein 160 vaccine-induced cellular and humoral immunity boosted by HIV-1(MN) recombinant glycoprotein 120 vaccine." AIDS Research and Human Retroviruses 15.2 (1999): 115-132.
PMID
10029244
Source
scival
Published In
AIDS Research and Human Retroviruses
Volume
15
Issue
2
Publish Date
1999
Start Page
115
End Page
132
DOI
10.1089/088922299311547

Immunization with envelope MN rgp120 vaccine in human immunodeficiency virus-infected pregnant women

Twenty-six human immunodeficiency virus (HIV) infected pregnant women participated in a placebo-controlled study of immunogenicity and safety of multiple doses of MN rgp120 vaccine over the last half of pregnancy. The women had CD4 lymphocyte counts >400/mm3, no AIDS-defining illness and normal pregnancies. Vaccination was well tolerated, with no significant local or systemic reactions in the women and no adverse outcomes in the infants attributable to the vaccine. Vaccination did not alter plasma RNA reverse transcriptase-polymerase chain reaction copy number; moreover, immunization was not associated with changes in CD4 counts or HIV binding and neutralization antibody titers. Infants were followed up until 18 months of age. Five of 26 infants (19%) were HIV infected, with infection occurring in children of both vaccinated and placebo women. Analysis of factors that influence transmission did not disclose associations with immunization status, viral load, CD4 count, or maternal viral neutralization titers.

Authors
Wright, P; Lambert, JS; Gorse, GJ; Hsieh, R-H; McElrath, MJ; Weinhold, K; Wara, DW; Anderson, EL; Keefer, MC; Jackson, S; Wagner, LJ; Francis, DP; Fast, PE; McNamara, J
MLA Citation
Wright, P, Lambert, JS, Gorse, GJ, Hsieh, R-H, McElrath, MJ, Weinhold, K, Wara, DW, Anderson, EL, Keefer, MC, Jackson, S, Wagner, LJ, Francis, DP, Fast, PE, and McNamara, J. "Immunization with envelope MN rgp120 vaccine in human immunodeficiency virus-infected pregnant women." Journal of Infectious Diseases 180.4 (1999): 1080-1088.
PMID
10479134
Source
scival
Published In
Journal of Infectious Diseases
Volume
180
Issue
4
Publish Date
1999
Start Page
1080
End Page
1088
DOI
10.1086/314985

Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers. NIAID AIDS Vaccine Evaluation Group.

OBJECTIVE: To determine the ability of live attenuated canarypox virus expressing HIV antigens to induce CD8+ cytotoxic T-cell responses and to prime for neutralizing antibody responses to boosting with purified recombinant gp120 subunit vaccine. DESIGN: A prospective, double-blind, randomized, immunogenicity and safety study was conducted in healthy adults at low risk for acquiring HIV infection and who were seronegative for HIV. METHODS: CD8+ cytotoxic T-cells directed against Env or Gag expressing target cells were measured after live recombinant canarypox-HIV-1 vaccine priming (vaccine given at days 0, 7, 14 and 21). Neutralizing antibodies were measured after subunit boosting (vaccine given at days 28 and 84). RESULTS: CD8+ CTL were induced in 64% of volunteers by the live recombinant canarypox-HIV-1 vaccine. All volunteers who received two doses of subunit vaccine after live recombinant canarypox priming developed neutralizing antibodies directed against laboratory strains of HIV-1 and seven out of eight volunteers tested developed neutralizing antibodies to the primary isolate, BZ167, but to none of eight other primary isolates. Unprimed controls had low or absent neutralizing antibodies after two doses of subunit vaccine. CONCLUSIONS: The live canarypox vector was safe, stimulated cytotoxic T-cells and primed for a vigorous neutralizing antibody response upon boosting with subunit gp120 vaccine. This vaccine combination should be evaluated further for inducing protection against HIV infection.

Authors
Belshe, RB; Gorse, GJ; Mulligan, MJ; Evans, TG; Keefer, MC; Excler, JL; Duliege, AM; Tartaglia, J; Cox, WI; McNamara, J; Hwang, KL; Bradney, A; Montefiori, D; Weinhold, KJ
MLA Citation
Belshe, RB, Gorse, GJ, Mulligan, MJ, Evans, TG, Keefer, MC, Excler, JL, Duliege, AM, Tartaglia, J, Cox, WI, McNamara, J, Hwang, KL, Bradney, A, Montefiori, D, and Weinhold, KJ. "Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers. NIAID AIDS Vaccine Evaluation Group." AIDS 12.18 (December 24, 1998): 2407-2415.
PMID
9875578
Source
pubmed
Published In
AIDS
Volume
12
Issue
18
Publish Date
1998
Start Page
2407
End Page
2415

Coadministration of zidovudine and interleukin-2 increases absolute CD4 cells in subjects with Walter Reed stage 2 human immunodeficiency virus infection: results of ACTG protocol 042.

Interleukin-2 (IL-2) can increase numbers of absolute CD4 cells in persons infected with the human immunodeficiency virus who are receiving antiretroviral therapy. Twenty-five subjects with > 400/mm3 absolute CD4 cells received zidovudine and low-dose intravenous or subcutaneous IL-2 (< or = 10(6) U/m2). Absolute CD4 cells increased significantly during IL-2 treatment, and 56% of the subjects achieved a maximal increase of > or = 500 cells/mm3. A dose-response relationship favored increasing IL-2 doses, and subcutaneous delivery offered greater increases than intravenous administration. Fifteen subjects had persistent increases of > or = 100 cells/mm3 6 weeks after IL-2 was discontinued. No changes occurred in delayed-type hypersensitivity or helper T cell responses to recall antigens. Cell-mediated cytotoxicities increased against Daudi cells. IL-2 was well tolerated and only 1 subject required dose reduction. Relatively low-dose IL-2 delivered by subcutaneous or intravenous routes may provide an important complement to antiretroviral therapy to increase absolute CD4 cells with the potential for less toxicity than with higher IL-2 doses.

Authors
Bartlett, JA; Berend, C; Petroni, GR; Ottinger, J; Tyler, DL; Pettinelli, C; Weinhold, KJ
MLA Citation
Bartlett, JA, Berend, C, Petroni, GR, Ottinger, J, Tyler, DL, Pettinelli, C, and Weinhold, KJ. "Coadministration of zidovudine and interleukin-2 increases absolute CD4 cells in subjects with Walter Reed stage 2 human immunodeficiency virus infection: results of ACTG protocol 042." J Infect Dis 178.4 (October 1998): 1170-1173.
PMID
9806053
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
178
Issue
4
Publish Date
1998
Start Page
1170
End Page
1173

Lymphokine-activated killer (LAK) cell anti-HIV-1 ADCC reactivity: a potential strategy for reduction of virus-infected cellular reservoirs.

Lymphocytes from HIV-1-seropositive and -seronegative individuals were examined to determine whether HIV-1 infection interfered with the ability to generate a lymphokine-activated killer (LAK) cell response. Following a 3-day ex vivo incubation in the presence of 1000 U/ml of recombinant interleukin-2, lymphocytes from seropositive individuals exhibited a LAK cell response which was equivalent to or greater than that of seronegative controls as measured against Daudi cell targets. LAK cells from seropositive and seronegative donors showed no specific cytolytic activity against gp120-coated or HIV-1-infected targets. However, in the presence of patient sera, significant levels of virus-specific LAK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) were observed. The level of this specific LAK cell-mediated ADCC was greater than that mediated under similar conditions by freshly isolated peripheral blood mononuclear cells. The greatest improvement in ADCC over baseline activity was seen with lymphocytes from AIDS patients after the 3-day ex vivo activation, suggesting that this patient population might benefit the most from adaptive LAK cell therapy.

Authors
Tyler, DS; Stanley, SD; Bartlett, JA; Bolognesi, DP; Weinhold, KJ
MLA Citation
Tyler, DS, Stanley, SD, Bartlett, JA, Bolognesi, DP, and Weinhold, KJ. "Lymphokine-activated killer (LAK) cell anti-HIV-1 ADCC reactivity: a potential strategy for reduction of virus-infected cellular reservoirs." J Surg Res 79.2 (October 1998): 115-120.
PMID
9758725
Source
pubmed
Published In
Journal of Surgical Research
Volume
79
Issue
2
Publish Date
1998
Start Page
115
End Page
120
DOI
10.1006/jsre.1998.5415

Safety and immunogenicity of an HLA-based HIV envelope polyvalent synthetic peptide immunogen. DATRI 010 Study Group. Division of AIDS Treatment Research Initiative.

OBJECTIVE: To evaluate the safety and immunogenicity of a polyvalent (PV) HIV envelope synthetic peptide immunogen, C4-V3. The immunogen comprised four peptides containing T-helper epitopes from the fourth constant region (C4) of gp120 of HIV-1MN, and T-helper, cytotoxic T-lymphocyte HLA-B7-restricted, and B-cell neutralizing epitopes from the gp120 third variable region (V3) of four clade B HIV-1 isolates, HIV-1MN, HIV-1RF, HIV-1EV91, and HIV-1Can0A. DESIGN: A pilot, Phase I controlled trial [Division of AIDS Treatment Research Initiative (DATRI) 010] conducted at a single center. METHODS: Ten HIV-infected, HLA-B7-positive patients with CD4 cells > 500 x 10(6)/l were enrolled. Eight patients received the C4-V3 PV immunogen emulsified in incomplete Freund's adjuvant in five intramuscular injections over 24 weeks, and two controls received incomplete Freund's adjuvant alone. All subjects were followed for 52 weeks. RESULTS: Four out of eight C4-V3 PV recipients generated at least fourfold rise in serum antibody titers to at least three immunogen peptides in contrast to none of the control subjects. Four out of eight C4-V3 PV recipients and none of the controls had an at least fourfold rise in neutralizing antibodies to either HIV-1MN, HIV-1RF, or HIV-1(4489-5) laboratory-adapted HIV isolates. 3H-Thymidine incorporation assays of peripheral blood mononuclear cells increased at least fivefold over the baseline stimulation index to at least one of the immunogen peptides in two consecutive post-immunization timepoints in five out of eight C4-V3 PV recipients versus none of the controls. CD4 cell counts and plasma HIV RNA levels did not change in patients who received either C4-V3 PV or adjuvant alone. Adverse events consisted primarily of grade 1 injection site reactions in six subjects (four C4-V3 recipients, two controls). CONCLUSIONS: C4-V3 PV synthetic peptides demonstrated both immunogenicity and safety in HIV-infected patients.

Authors
Bartlett, JA; Wasserman, SS; Hicks, CB; Dodge, RT; Weinhold, KJ; Tacket, CO; Ketter, N; Wittek, AE; Palker, TJ; Haynes, BF
MLA Citation
Bartlett, JA, Wasserman, SS, Hicks, CB, Dodge, RT, Weinhold, KJ, Tacket, CO, Ketter, N, Wittek, AE, Palker, TJ, and Haynes, BF. "Safety and immunogenicity of an HLA-based HIV envelope polyvalent synthetic peptide immunogen. DATRI 010 Study Group. Division of AIDS Treatment Research Initiative." AIDS 12.11 (July 30, 1998): 1291-1300.
PMID
9708408
Source
pubmed
Published In
AIDS
Volume
12
Issue
11
Publish Date
1998
Start Page
1291
End Page
1300

Herpesvirus saimiri transformation of HIV type 1 suppressive CD8+ lymphocytes from an HIV type 1-infected asymptomatic individual.

CD8+ T lymphocytes from HIV+ individuals can potently suppress HIV-1 replication in a noncytolytic manner. This suppression appears to be multifactorial and the molecules contributing have not been fully elucidated. As an approach to this question we used herpesvirus saimiri (HVS) to transform CD8+ T lymphocytes from an HIV+ asymptomatic donor to a continuously growing, activation-independent, IL-2-dependent phenotype. The transformed cell population, termed CD8(HVS), had an activated phenotype, contained HVS sequences, did not shed infectious HVS virus, and was polyclonal. The CD8(HVS) cells, despite the absence of detectable CTL activity, potently suppressed HIV-1 production by both autologous and heterologous CD4+ cells from infected donors. The CD8(HVS) cells in coculture also suppressed virus production from PBMCs acutely infected with syncytium-inducing (SI) strains or NSI primary isolates of HIV-1. The supernatants from the CD8(HVS) cells and their concentrates derived from these supernatants were suppressive to NSI primary isolates of HIV-1 but not to SI strains. Fractionation of these concentrates showed that the suppressive activity was associated with low molecular mass (6500- to 19,300-Da) protein species. Western blotting and ELISA indicated that the CC chemokines MIP-1alpha, MIP-1beta, and RANTES were present in these fractions. Antibody-blocking studies with antibodies to the CC chemokines indicated that a significant portion of the soluble HIV-suppressive activity was due to these molecules. However, these experiments also suggested the inhibitory activity of the CD8(HVS) cells in coculture is not due exclusively to the CC chemokines. The HVS-transformed cells provide a useful tool for the study of noncytolytic CD8+ T lymphocyte-mediated suppression of HIV-1.

Authors
Lacey, SF; Weinhold, KJ; Chen, CH; McDanal, C; Oei, C; Greenberg, ML
MLA Citation
Lacey, SF, Weinhold, KJ, Chen, CH, McDanal, C, Oei, C, and Greenberg, ML. "Herpesvirus saimiri transformation of HIV type 1 suppressive CD8+ lymphocytes from an HIV type 1-infected asymptomatic individual." AIDS Res Hum Retroviruses 14.6 (April 10, 1998): 521-531.
PMID
9566555
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
14
Issue
6
Publish Date
1998
Start Page
521
End Page
531
DOI
10.1089/aid.1998.14.521

The CD8+ cell non-cytotoxic, anti-HIV response is associated with protection in HIV-exposed, uninfected individuals

Several multiply HIV-exposed, uninfected cohorts were studied for evidence of correlates of protective immunity. This uninfected high risk population was comprised of the IV drug-sharing and/or sexual partners of infected individuals. Genotyping of cells from these HIV-exposed individuals revealed that 29% (14/50) were heterozygous and 4% (2/50) homozygous for the previously identified mutant CCR5 allele (delts32). In vitro infection studies showed that the CD4+ cells from all the individuals tested were susceptible to infection with primary virus strains, including those isolated from their infected partners. None of the high risk individuals tested exhibited evidence of HIV-specific cytotoxic T-lymphocyte responses. However, 50 to 100% of the high risk individuals did manifest a strong CD8+ cell, non-cytotoxic anti-HIV response against either highly cytopathic laboratory virus strains or slower-growing laboratory and primary virus isolates, respectively. This type of immune response was absent in unexposed control subjects. These data demonstrate that high risk individuals remain HIV negative despite having target lymphocytes which are sensitive to HIV infection. Prior exposure of these individuals to HIV appears to induce a protective CD8+ cell noncytotoxic antiviral response not seen in unexposed individuals.

Authors
Stranford, S; Skurnick, J; Louria, D; Osmond, D; Chang, S-Y; Sninsky, J; Ferrari, G; Weinhold, K; Lindquist, C; Levy, J
MLA Citation
Stranford, S, Skurnick, J, Louria, D, Osmond, D, Chang, S-Y, Sninsky, J, Ferrari, G, Weinhold, K, Lindquist, C, and Levy, J. "The CD8+ cell non-cytotoxic, anti-HIV response is associated with protection in HIV-exposed, uninfected individuals." 1998.
Source
scival
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
12
Issue
4
Publish Date
1998
Start Page
A295

Direct and indirect estimates of HIV-1 incidence in a high-prevalence population

HIV incidence data, necessary for the planning and evaluation of national AIDS control programs, are difficult to obtain directly. In this study, HIV-1 incidence in Trinidad was estimated in a population known to be at high risk: heterosexuals attending a sexually transmitted disease clinic in Port of Spain in 1987-95. HIV incidence estimates were obtained from serial cross-sectional studies of HIV-1 prevalence (n = 3625), passive follow-up of clinic recidivists (n = 98), modeling of early markers of HIV-1 infection (p24 antigen screening) (n = 12,154), and a cohort study of seronegative genital ulcer disease cases (n = 196). Measuring incidence density in genital ulcer disease cases directly gave the highest estimate: 6.9% per year. Screening for the detection of early HIV-1 markers yielded an incidence of 5.0% per year, while estimating incidence from serial cross-sectional prevalence data and clinic recidivists provided estimates of 3.5% and 4.5%, respectively. Although these estimates come from groups within the clinic population with differential HIV-1 risk, they were internally consistent. These findings suggest that indirect estimates of incidence based on prevalence data can provide accurate surrogates of true HIV incidence and may be used to target suitable populations for cohort studies.

Authors
Cleghorn, PR; Jack, N; Murphy, JR; Edwards, J; Mahabir, B; Paul, R; O'Brien, T; Greenberg, M; Weinhold, K; Bartholomew, C; Brookmeyer, R; Blattner, WA
MLA Citation
Cleghorn, PR, Jack, N, Murphy, JR, Edwards, J, Mahabir, B, Paul, R, O'Brien, T, Greenberg, M, Weinhold, K, Bartholomew, C, Brookmeyer, R, and Blattner, WA. "Direct and indirect estimates of HIV-1 incidence in a high-prevalence population." American Journal of Epidemiology 147.9 (1998): 834-839.
PMID
9583713
Source
scival
Published In
American Journal of Epidemiology
Volume
147
Issue
9
Publish Date
1998
Start Page
834
End Page
839

Cytotoxic T cell and neutralizing antibody responses to human immunodeficiency virus type 1 envelope with a combination vaccine regimen

Effective human immunodeficiency virus (HIV) vaccination may require induction of neutralizing antibodies (NAs) and CD8+ cytotoxic T lymphocytes (CTL) to prevent transmission and control early infection. Recombinant envelope proteins induce NAs but rarely CD8+ CTL responses, and vaccinia vectors containing HIV-1 envelope elicit CD8+ cytotoxicity but few NAs. To benefit from both approaches, 56 vaccinia-naive subjects were randomized to a regimen of priming with recombinant vaccinia gp160(LA1) and boosting with recombinant gp120(SF-2), gp120(LA-1), gp120(MN), or gp160(MN). Of 51 persons for whom assays were done, 26 demonstrated envelope-specific CTL. Boosting with gp120, compared with gp160, elicited significantly more NAs and CD4- blocking antibodies. Neutralization of the homologous and heterologous HIV-1 laboratory strains occurred in all subjects receiving vac/env and gp120 and was detectable in 91% of the subjects for >6 months. Thus, vaccine regimens in which one component elicits primarily CTL and the other NAs offer promise for the development of an effective HIV-1 vaccine strategy.

Authors
Corey, L; McElrath, MJ; Weinhold, K; Matthews, T; Stablein, D; Graham, B; Keefer, M; Schwartz, D; Gorse, G
MLA Citation
Corey, L, McElrath, MJ, Weinhold, K, Matthews, T, Stablein, D, Graham, B, Keefer, M, Schwartz, D, and Gorse, G. "Cytotoxic T cell and neutralizing antibody responses to human immunodeficiency virus type 1 envelope with a combination vaccine regimen." Journal of Infectious Diseases 177.2 (1998): 301-309.
PMID
9466515
Source
scival
Published In
Journal of Infectious Diseases
Volume
177
Issue
2
Publish Date
1998
Start Page
301
End Page
309

Modulation of immunologic responses to HIV-1(MN) recombinant gp160 vaccine by dose and schedule of administration

The safety and immunogenicity of HIV-1(MN) recombinant gp160 (MN rgp160) vaccine in healthy, uninfected volunteers was tested in a double-blind study with a factorial design. By random assignment, 20 volunteers received three 200 μg doses of MN rgp160 and four volunteers received placebo at day 0, 28 and 168 or 0, 56, and 224. Of the 24 volunteers, 16 received 200 μg or 800 μg of MN rgp160 and two received placebo at day 532 (month 18). The vaccine was safe. It induced T cell memory measured by Th1 cytokine production and lymphocyte proliferation and serum anti-MN rgp160 IgG (all subclasses) and IgA antibodies. Fifteen of 20 vaccinees developed neutralizing antibody. The regimen including immunizations on days 0, 28, and 168 followed by the 800 μg fourth dose was most immunogenic.

Authors
Gorse, GJ; McElrath, MJ; Matthews, TJ; Hsieh, R-H; Belshe, RB; Corey, L; Frey, SE; Kennedy, DJ; Walkerl, MC; Eibl, MM; Schwartz, D; Clemen, ML; Mulligan, M; Mestecky, J; Jackson, S; Hook, E; Keefer, MC; Dolin, R; Graham, BS; Wright, P; Weinhold, K; Bolognesi, D; Savarese, B; McNamara, JG; Fast, PE
MLA Citation
Gorse, GJ, McElrath, MJ, Matthews, TJ, Hsieh, R-H, Belshe, RB, Corey, L, Frey, SE, Kennedy, DJ, Walkerl, MC, Eibl, MM, Schwartz, D, Clemen, ML, Mulligan, M, Mestecky, J, Jackson, S, Hook, E, Keefer, MC, Dolin, R, Graham, BS, Wright, P, Weinhold, K, Bolognesi, D, Savarese, B, McNamara, JG, and Fast, PE. "Modulation of immunologic responses to HIV-1(MN) recombinant gp160 vaccine by dose and schedule of administration." Vaccine 16.5 (1998): 493-506.
PMID
9491504
Source
scival
Published In
Vaccine
Volume
16
Issue
5
Publish Date
1998
Start Page
493
End Page
506
DOI
10.1016/S0264-410X(97)80003-5

Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1(MN) gp120, HIV-1(SF2) recombinant gp120, or both vaccines in seronegative adults

A safety and immunogenicity trial was conducted in vaccinia-immune and vaccinia-naive human immunodeficiency virus (HIV)-uninfected adults who were randomized to receive 106 or 107 TCID50 of canarypox (ALVAC) vector expressing HIV-1(MN) gp160 or 105.5 TCID50 of ALVAC-rabies virus glycoprotein control at 0 and 1 or 2 months and ALVAC-gp160 or 50 μg of HIV- 1(SF2) recombinant (r) gp120 in microfluidized emulsion at 9 and 12 months; others received rgp120 at 0, 1, 6, and 12 months. All vaccines were well- tolerated. Neither vaccinia-immune status before vaccination nor ALVAC dose affected HIV immune responses. HIV-1(MN) and HIV-1(SF2) neutralizing antibodies were detected more often (100%) in ALVAC-gp160/rgp120 recipients than in recipients of ALVAC-gp160 (<65%) or rgp120 (89%) alone. ALVAC- gp160/rgp120 also elicited more frequent HIV V3-specific and fusion- inhibition antibodies, antibody-dependent cellular cytotoxicity, lymphoproliferation, and cytotoxic CD8+ T cell activity than did either vaccine alone. Trials with ALVAC expressing additional HIV components and rgp120 are underway.

Authors
Clements-Mann, ML; Weinhold, K; Matthews, TJ; Graham, BS; Gorse, GJ; Keefer, MC; McElrath, MJ; Hsieh, R-H; Mestecky, J; Zolla-Pazner, S; Mascola, J; Schwartz, D; Siliciano, R; Corey, L; Wright, PF; Belshe, R; Dolin, R; Jackson, S; Xu, S; Fast, P; Walker, MC; Stablein, D; Excler, J-L; Tartaglia, J; Duliege, A-M; Sinangil, F; Paoletti, E
MLA Citation
Clements-Mann, ML, Weinhold, K, Matthews, TJ, Graham, BS, Gorse, GJ, Keefer, MC, McElrath, MJ, Hsieh, R-H, Mestecky, J, Zolla-Pazner, S, Mascola, J, Schwartz, D, Siliciano, R, Corey, L, Wright, PF, Belshe, R, Dolin, R, Jackson, S, Xu, S, Fast, P, Walker, MC, Stablein, D, Excler, J-L, Tartaglia, J, Duliege, A-M, Sinangil, F, and Paoletti, E. "Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1(MN) gp120, HIV-1(SF2) recombinant gp120, or both vaccines in seronegative adults." Journal of Infectious Diseases 177.5 (1998): 1230-1246.
PMID
9593008
Source
scival
Published In
Journal of Infectious Diseases
Volume
177
Issue
5
Publish Date
1998
Start Page
1230
End Page
1246

Cellular immune responses to candidate AIDS vaccines

Authors
Weinhold, KJ; Humphrey, W; Corr, K; Johnson, J; West, M; Wiggins, C; Jones, S; Ottinger, J; Blanks, M; Ferrari, G
MLA Citation
Weinhold, KJ, Humphrey, W, Corr, K, Johnson, J, West, M, Wiggins, C, Jones, S, Ottinger, J, Blanks, M, and Ferrari, G. "Cellular immune responses to candidate AIDS vaccines." 1998.
Source
wos-lite
Published In
11E COLLOQUE DES CENT GARDES
Publish Date
1998
Start Page
167
End Page
175

Replication-defective canarypox (ALVAC) vectors effectively activate anti-human immunodeficiency virus-1 cytotoxic T lymphocytes present in infected patients: implications for antigen-specific immunotherapy.

In the attempt to develop immunotherapeutic strategies for acquired immunodeficiency syndrome capable of activating effector cells in an antigen-specific manner while maintaining the broadest possible T-cell repertoire, we evaluated two canarypox (ALVAC)-based vectors for their capacity to induce ex vivo activation/expansion of human immunodeficiency virus (HIV)-specific CD8+ cytotoxic lymphocyte precursors (CTLp) obtained from HIV-1-infected donors. These two vectors, vCP205 encoding HIV-1 gp120 + TM (28 amino acid transmembrane anchor sequence) in addition to Gag/protease and vCP300 encoding gp120 + Gag/protease as well as Nef and Pol CTL determinants, are pancytotropic but replication incompetent in mammalian cells. Bulk peripheral blood mononuclear cells (PBMCs) or enriched CD8+ T cells were stimulated for 10 days with autologous ALVAC-infected PBMCs in the presence of different cytokine combinations (interleukin-2 [IL-2], IL-4, IL-7, and IL-12). Activation by ALVAC constructs was highly antigen-specific, because vCP205 elicited only Env and Gag CTL, whereas vCP300 elicited broader reactivities against Env, Gag, Pol, and Nef determinants. The ALVAC activation of CTLp was IL-2 dependent and enhanced by the addition of IL-7, whereas IL-4 and IL-12 failed to augment cytotoxic reactivities elicited by these constructs. The expansion of enriched CD8+ T cells after activation with vCP300 was higher in patients with CD4 counts greater than 400 cells/microL. Two rounds of in vitro stimulation (IVS) with vCP300 resulted in nearly an eightfold expansion of CD8+ lymphocytes over a 25-day period. After the second IVS, an average 3.2-fold increase among the different antigen-specific CTL frequencies was achieved. These studies clearly show that HIV-recombinant ALVAC vectors represent powerful polyvalent antigenic stimuli for activation and expansion of the CD8 lymphocyte response that occurs as a result of HIV infection.

Authors
Ferrari, G; Berend, C; Ottinger, J; Dodge, R; Bartlett, J; Toso, J; Moody, D; Tartaglia, J; Cox, WI; Paoletti, E; Weinhold, KJ
MLA Citation
Ferrari, G, Berend, C, Ottinger, J, Dodge, R, Bartlett, J, Toso, J, Moody, D, Tartaglia, J, Cox, WI, Paoletti, E, and Weinhold, KJ. "Replication-defective canarypox (ALVAC) vectors effectively activate anti-human immunodeficiency virus-1 cytotoxic T lymphocytes present in infected patients: implications for antigen-specific immunotherapy." Blood 90.6 (September 15, 1997): 2406-2416.
PMID
9310492
Source
pubmed
Published In
Blood
Volume
90
Issue
6
Publish Date
1997
Start Page
2406
End Page
2416

Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers.

A fundamental goal of current strategies to develop an efficacious vaccine for AIDS is the elicitation of broadly reactive cytotoxic T lymphocyte (CTL) reactivities capable of destroying virally infected targets. Recent application of recombinant canarypox ALVAC/HIV-1 vectors as vaccine immunogens in HIV-1,-noninfected volunteers has produced CTL responses in a significant number of vaccinees. Using a newly developed targeting strategy, we examined the capacity of vaccine-induced CTL to lyse autologous targets infected with a diverse group of viral isolates. CTL derived from recipients of a canarypox ALVAC/HIV-1 gp160 (MN) vaccine were found capable of lysing autologous CD4+ lymphoblasts infected with the prototypic LAI strain of HIV-1. When tested against autologous targets infected with primary HIV-1 isolates representing genetically diverse viral clades, CTL from ALVAC/gp160 recipients showed both a broad pattern of cytolysis in which viruses from all clades tested were recognized as well as a highly restricted pattern in which no primary isolates, including clade B, were lysed. Differences in the HLA haplotypes of the volunteers immunized with the envelope vector might be a major determinant of the relative breadth of their CTL response. In contrast to ALVAC/gp160 vaccinees, recipients of the ALVAC/HIV-1 immunogen containing envelope as well as gag and protease genes consistently had CTL reactivities effective against a spectrum of primary isolate-infected targets. These studies demonstrate for the first time that clade B-based canarypox vaccines can elicit broad CTL reactivities capable of recognizing viruses belonging to genetically diverse HIV-1 clades. The results also reinforce the impact of viral core elements in the vaccine as well as the pattern of major histocompatibility complex class I allelic expression by the vaccine recipient in determining the relative breadth of the cellular response.

Authors
Ferrari, G; Humphrey, W; McElrath, MJ; Excler, JL; Duliege, AM; Clements, ML; Corey, LC; Bolognesi, DP; Weinhold, KJ
MLA Citation
Ferrari, G, Humphrey, W, McElrath, MJ, Excler, JL, Duliege, AM, Clements, ML, Corey, LC, Bolognesi, DP, and Weinhold, KJ. "Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers." Proc Natl Acad Sci U S A 94.4 (February 18, 1997): 1396-1401.
PMID
9037064
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
94
Issue
4
Publish Date
1997
Start Page
1396
End Page
1401

HIV type 1 vaccine-induced cytotoxic T cell responses in phase I clinical trials: detection, characterization, and quantitation.

Authors
McElrath, MJ; Siliciano, RF; Weinhold, KJ
MLA Citation
McElrath, MJ, Siliciano, RF, and Weinhold, KJ. "HIV type 1 vaccine-induced cytotoxic T cell responses in phase I clinical trials: detection, characterization, and quantitation." AIDS Res Hum Retroviruses 13.3 (February 10, 1997): 211-216. (Review)
PMID
9115806
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
13
Issue
3
Publish Date
1997
Start Page
211
End Page
216
DOI
10.1089/aid.1997.13.211

Noncytolytic CD8 T cell-mediated suppression of HIV replication.

Authors
Greenberg, ML; Lacey, SF; Chen, CH; Bolognesi, DP; Weinhold, KJ
MLA Citation
Greenberg, ML, Lacey, SF, Chen, CH, Bolognesi, DP, and Weinhold, KJ. "Noncytolytic CD8 T cell-mediated suppression of HIV replication." Springer Semin Immunopathol 18.3 (1997): 355-369. (Review)
PMID
9089954
Source
pubmed
Published In
Springer seminars in immunopathology
Volume
18
Issue
3
Publish Date
1997
Start Page
355
End Page
369

HIV infection--induced posttranslational modification of T cell signaling molecules associated with disease progression.

In attempt to elucidate the mechanism of the HIV infection induced T cell unresponsiveness, we studied signal-transducing molecules proximal to the T cell receptor (TCR) in T lymphocytes of HIV-infected individuals. Total amounts of protein tyrosine kinases (PTKs) Lck, Fyn, and ZAP-70 and the zeta chain of the TCR were found significantly decreased in T cells of symptomatic/AIDS patients as well as in T cells of individuals in acute and early asymptomatic stages of HIV infection. Unexpectedly, the detection of Lck, Fyn, and ZAP-70 was reversed after the treatment of cell lysates with dithiothreitol. This suggests that PTKs Lck, Fyn, and ZAP-70 were modified by a mechanism altering the status of sulfhydryl groups. Moreover, this mechanism seems to affect selectively T cells of HIV infected patients since B cell PTKs Syk and Lyn were detected structurally and functionally intact. Interestingly, similar alterations of signaling molecules were not detected in T cells of HIV-infected long-term asymptomatic individuals. Modification of T cell PTKs may thus underlie the HIV-induced impairment of lymphocyte function and may potentially predict disease progression.

Authors
Stefanová, I; Saville, MW; Peters, C; Cleghorn, FR; Schwartz, D; Venzon, DJ; Weinhold, KJ; Jack, N; Bartholomew, C; Blattner, WA; Yarchoan, R; Bolen, JB; Horak, ID
MLA Citation
Stefanová, I, Saville, MW, Peters, C, Cleghorn, FR, Schwartz, D, Venzon, DJ, Weinhold, KJ, Jack, N, Bartholomew, C, Blattner, WA, Yarchoan, R, Bolen, JB, and Horak, ID. "HIV infection--induced posttranslational modification of T cell signaling molecules associated with disease progression." J Clin Invest 98.6 (September 15, 1996): 1290-1297.
PMID
8823293
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
98
Issue
6
Publish Date
1996
Start Page
1290
End Page
1297
DOI
10.1172/JCI118915

Long-term follow-up of symptomatic HIV-infected patients originally randomized to early versus later zidovudine treatment; report of a Veterans Affairs Cooperative Study. VA Cooperative Study Group on AIDS Treatment.

Following a 4-year controlled trial comparing early and later zidovudine treatment, we conducted an additional 3-year follow-up. Of the original 338 patients, 275 participated. Clinical outcome measures were AIDS and death. In the early therapy group (n = 170), 67 patients progressed to AIDS compared with 85 in the later therapy group (n = 168); the relative risk (RR) comparing early with later therapy was 0.72% (95% confidence interval [CI] 0.52-0.99; p = 0.044). The early therapy group had 74 deaths compared with 73 in the later therapy (RR = 0.98; 95% CI, 0.71-1.36; p = 0.91). The early group had a peak CD4+ count increase at 1-2 months and a delay of 1 year before CD4+ counts fell below baseline. For patients who received zidovudine for more than the median duration (20.3 months) before their first AIDS diagnosis, the RR for death was 2.08 (95% CI, 1.36-3.19, p = 0.001). Additional factors independently associated with poor prognosis following AIDS were a CD4+ count of < 100 cells/mm3 and increased severity of the first AIDS diagnosis, whereas use of another antiretroviral agent was associated with improved survival. We conclude that early zidovudine therapy delays progression to AIDS but does not affect survival. Patients who progress to AIDS while on prolonged zidovudine monotherapy many benefit from a change to other antiretroviral therapy(ies).

Authors
Simberkoff, MS; Hartigan, PM; Hamilton, JD; Day, PL; Diamond, GR; Dickinson, GM; Drusano, GL; Egorin, MJ; George, WL; Gordin, FM; Hawkes, CA; Jensen, PC; Kilmas, NG; Labriola, AM; O'Brien, WA; Oster, CN; Weinhold, KJ; Wray, NP; Pazner, SB
MLA Citation
Simberkoff, MS, Hartigan, PM, Hamilton, JD, Day, PL, Diamond, GR, Dickinson, GM, Drusano, GL, Egorin, MJ, George, WL, Gordin, FM, Hawkes, CA, Jensen, PC, Kilmas, NG, Labriola, AM, O'Brien, WA, Oster, CN, Weinhold, KJ, Wray, NP, and Pazner, SB. "Long-term follow-up of symptomatic HIV-infected patients originally randomized to early versus later zidovudine treatment; report of a Veterans Affairs Cooperative Study. VA Cooperative Study Group on AIDS Treatment." J Acquir Immune Defic Syndr Hum Retrovirol 11.2 (February 1, 1996): 142-150.
PMID
8556396
Source
pubmed
Published In
Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association
Volume
11
Issue
2
Publish Date
1996
Start Page
142
End Page
150

A dose-ranging study of a prototype synthetic HIV-1MN V3 branched peptide vaccine. The National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group.

A phase I double-blind trial was done to examine the safety and immunogenicity of a prototype synthetic human immunodeficiency virus type 1 MN strain (HIV-1MN) third variable region domain (V3) branched peptide vaccine in HIV-1-uninfected healthy adult volunteers. Subjects were randomly assigned to receive 20, 100, or 500 micrograms of vaccine or alum adjuvant control on days 0, 28, and 168. The vaccine was well-tolerated and appeared safe. Induction of binding antibody to V3 MN branched peptide was vaccine dose-related and was detectable in 9 of 10 subjects in the highest-vaccine-dose group. HIV-1MN-neutralizing antibody was detected after the third 500-micrograms dose in 8 of 10 subjects at the 90% neutralization end point. V3 MN peptide stimulated lymphocyte proliferation in 15 (75%) of 20 subjects after vaccination. In conclusion, this prototype vaccine was safe and it induced humoral and cell-mediated immune responses.

Authors
Gorse, GJ; Keefer, MC; Belshe, RB; Matthews, TJ; Forrest, BD; Hsieh, RH; Koff, WC; Hanson, CV; Dolin, R; Weinhold, KJ; Frey, SE; Ketter, N; Fast, PE
MLA Citation
Gorse, GJ, Keefer, MC, Belshe, RB, Matthews, TJ, Forrest, BD, Hsieh, RH, Koff, WC, Hanson, CV, Dolin, R, Weinhold, KJ, Frey, SE, Ketter, N, and Fast, PE. "A dose-ranging study of a prototype synthetic HIV-1MN V3 branched peptide vaccine. The National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group." J Infect Dis 173.2 (February 1996): 330-339.
PMID
8568293
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
173
Issue
2
Publish Date
1996
Start Page
330
End Page
339

MAGE-1-specific precursor cytotoxic T-lymphocytes present among tumor-infiltrating lymphocytes from a patient with breast cancer: characterization and antigen-specific activation.

A potential target for development of tumor-specific immunotherapeutic strategies is the MAGE-1 gene. We have utilized a recently developed recombinant canarypox (ALVAC) virus vector containing the MAGE-1 gene (vCP235) to activate CTLs from a breast cancer patient bearing a MAGE-1+ tumor. Tumor-infiltrating lymphocytes (TILs) obtained from the tumor of a patient were stimulated in vitro with irradiated autologous peripheral blood mononuclear cells acutely infected with the vCP235 construct. These TILs preferentially expanded approximately 6-fold over a 16-day culture period and specifically recognized an allogeneic transformed B-cell line acutely infected with a vaccinia-MAGE-1 recombinant targeting vector (vP1188) in the context of HLA-A2 and/or B7. TCR V beta analysis of in vitro expanded T cells by a quantitative multiprobe RNase protection assay revealed preferential expansion of TCR V beta 6.3 and V beta 6.4. In addition, homologous T-cell receptor beta CDR3 joining sequences were found in the in vitro stimulated cultures. These results suggest that tumor antigen-specific, MHC-restricted CTLs may be derived from precursor CTLs present in TILs obtained from patients with MAGE-1+ tumors by in vitro stimulation with recombinant avipox MAGE-1 virus-infected autologous cells. Collectively, these findings provide a rationale for tumor-associated antigen-based immunization as a means of activating precursor CTLs residing in patients with tumors expressing defined tumor-associated antigens such as MAGE-1.

Authors
Toso, JF; Oei, C; Oshidari, F; Tartaglia, J; Paoletti, E; Lyerly, HK; Talib, S; Weinhold, KJ
MLA Citation
Toso, JF, Oei, C, Oshidari, F, Tartaglia, J, Paoletti, E, Lyerly, HK, Talib, S, and Weinhold, KJ. "MAGE-1-specific precursor cytotoxic T-lymphocytes present among tumor-infiltrating lymphocytes from a patient with breast cancer: characterization and antigen-specific activation." Cancer Res 56.1 (January 1, 1996): 16-20.
PMID
8548758
Source
pubmed
Published In
Cancer Research
Volume
56
Issue
1
Publish Date
1996
Start Page
16
End Page
20

Safety and Immimogenicity of a Candidate HIV-1 Vaccine in Healthy Adults: Recombinant Glycoprotein (rgp) 120: A Randomized, Double-Blind Trial

Objective: To evaluate the safety and immunogenicity of recombinant glycoprotein (rgp) 120, a candidate vaccine for the human immunodeficiency virus (HIV), formulated with a novel adjuvant, MF59, with or without a biological response modifier, MTP-PE. Design: Multicenter, double-blind, randomized trial. Setting: University medical centers. Participants: 49 healthy, HIV-seronegative volunteers 18 to 60 years of age who were at low risk for HIV type 1 (HIV-1) infection. Interventions: In part A of the study, 32 participants were randomly assigned to receive either 15 μg of rgp120 in MF59, 15 μg of rgp120 in MF59 plus 50 μg of MTP-PE, 50 μg of rgp120 in MF59, or 50 μg of rgp120 in MF59 plus 50 μg of MTP-PE. Participants were vaccinated at 0, 1, 6, and 12 to 18 months. In part B, 17 participants were randomly assigned to receive five monthly injections of either 50 μg of rgp120 in MF59 or MF59 alone followed by a booster injection at 12 to 18 months. Main Outcome Measures: Local and systemic reactions; laboratory measures of hepatic, renal, immunologic, and bone marrow toxicity; and HIV-specific serologic and cell-mediated immune responses. Results: 13 patients in part A received 50-μg doses of rgp120; type-specific neutralizing antibody responses against the SF-2 strain of HIV-1 (HIV-1/SF-2) were induced in all 13. Nine of the 13 had crossreactive neutralizing activity against the MN strain of HIV-1 (HIV-1/MN), and 2 had crossreactive neutralizing activity against the IIIB strain of HIV-1 (HIV-1/IIIB). Twelve patients had type-specific fusion inhibition activity; only 1 had crossreactive fusion inhibition activity against HIV-1/MN. The monthly vaccination schedule used in part B resulted in decreased antibody titers, indicating that a rest period in the schedule is necessary for maximal immunogenicity. Lymphoproliferative responses against gp120 were induced in all vaccine recipients. The stimulation index to gp120 was persistently greater than 15 for 6 months after the last booster vaccination was given. CD8+ cytotoxic T-lymphocyte activity was detected in 1 of the 11 participants tested. Vaccine that contained MTP-PE caused a greater number of moderate or severe local and systemic reactions (of 16 participants, 4 had local reactions and 13 had systemic reactions) than did vaccine formulated with MF59 alone (of 16 participants, 7 had local reactions [P < 0.01] and 0 had systemic reactions [P < 0.001]). Conclusions: The SF-2 rgp120 vaccine is safe and immunogenic. Three vaccinations with rgp120 in MF59 can induce type-specific and crossreactive neutralizing antibody against B-subtype laboratory strains of HIV-1. Human immunodeficiency virus-specific lymphoproliferative responses were induced in all vaccinated participants, and CD8+ cytotoxic T-lymphocyte activity was shown in one participant. A trend toward the augmentation of lymphoproliferative and humoral responses by MTP-PE was seen in the participants receiving 15 μg of rgp120. However, MTP-PE caused a statistically significant increase in the incidence of local and systemic side effects, which was felt to outweigh the small increase in immunogenicity provided by this biological response modifier in an otherwise well-tolerated vaccine.

Authors
Graham, BS; Keefer, MC; McElrath, MJ; Gorse, GJ; Schwartz, DH; Weinhold, K; Matthews, TJ; Esterlitz, JR; Sinangil, F; Fast, PE; Wright, PF; Dolin, R; Corey, L; Belshe, RB; Clements, ML; Bolognesi, DP; Stablein, DM; Chernoff, D; Duliège, AM; Walker, CM
MLA Citation
Graham, BS, Keefer, MC, McElrath, MJ, Gorse, GJ, Schwartz, DH, Weinhold, K, Matthews, TJ, Esterlitz, JR, Sinangil, F, Fast, PE, Wright, PF, Dolin, R, Corey, L, Belshe, RB, Clements, ML, Bolognesi, DP, Stablein, DM, Chernoff, D, Duliège, AM, and Walker, CM. "Safety and Immimogenicity of a Candidate HIV-1 Vaccine in Healthy Adults: Recombinant Glycoprotein (rgp) 120: A Randomized, Double-Blind Trial." Annals of Internal Medicine 125.4 (1996): 270-279.
PMID
8678389
Source
scival
Published In
Annals of Internal Medicine
Volume
125
Issue
4
Publish Date
1996
Start Page
270
End Page
279

Safety and immunogenicity of Env 2-3, a human immunodeficiency virus type 1 candidate vaccine, in combination with a novel adjuvant, MTP-PE/MF59

We investigated the safety and immunogenicity of a candidate HIV-1 vaccine, Env 2-3 (Chiron Biocine Co.), in combination with an adjuvant emulsion, MF59, with or without an additional immune modulator, MTP-PE, in 78 healthy HIV-1-seronegative adults. Sixteen subjects participated in a dose escalation study of MTP-PE in MF59 without Env 2-3, given at 0 and 1 months; 48 subjects participated in a study of a fixed dose of 30 μg of Env 2-3 in MF59 with increasing doses of MTP-PE (0, 5, 10, 25, 50, and 100 μg), and 14 subjects participated in a study of 100 μg of Env 2-3 in MF59 without MTP- PE. Subjects were assigned to study groups under a randomized, double-blind allocation. Subjects received immunization at 0, 1, and 6 months, and had the option of receiving a fourth dose at 12-18 months. Env 2-3 in MTP-PE/MF59 was associated with significant reactogenicity, in that severe, although self- limited systemic and/or local reactions occurred in 15 of 30 vaccinees. In contrast, Env 2-3 in MF59 without MTP-PE was relatively well tolerated, and severe local and/or systemic reactions occurred in only 2 of 18 subjects. Env 2-3 stimulated serum antibodies to HIV-1 envelope protein (gp120) as detected by Western blot in 39 of 43 subjects and to HIV-1 virus lysate by EIA in 28 of 43 subjects after three injections. The majority of subjects also developed EIA antibodies to recombinant gp120 (SF-2), gp120 (LAI), and V3 peptide (SF-2). Neutralizing antibodies to the homologous SF-2 strain developed in 30 of 43 and 27 of 34 subjects, and fusion inhibition antibodies in 25 of 43 and 15 of 36 subjects after three and four injections, respectively. Lymphoproliferative responses to the immunogen, Env 2-3, were observed in over 80% of the vaccinees examined, and CD4+ cytotoxic T cell activity directed against HIV-1 was noted transiently in 2 of 20 vaccinees. Addition of MTP-PE to Env 2-3 or increasing the dose of Env 2-3 from 30 to 100 μg did not augment immunogenicity. Env 2-3 in MF59 was well tolerated and immunogenic in HIV-1-seronegative individuals. The addition of MTP-PE significantly increased reactogenicity, but had little, if any, effect on immunogenicity.

Authors
Keefer, MC; Graham, BS; McElrath, MJ; Matthews, TJ; Stablein, DM; Corey, L; Wright, PF; Lawrence, D; Fast, PE; Weinhold, K; Hsieh, R-H; Chernoff, D; Dekker, C; Dolin, R
MLA Citation
Keefer, MC, Graham, BS, McElrath, MJ, Matthews, TJ, Stablein, DM, Corey, L, Wright, PF, Lawrence, D, Fast, PE, Weinhold, K, Hsieh, R-H, Chernoff, D, Dekker, C, and Dolin, R. "Safety and immunogenicity of Env 2-3, a human immunodeficiency virus type 1 candidate vaccine, in combination with a novel adjuvant, MTP-PE/MF59." AIDS Research and Human Retroviruses 12.8 (1996): 683-693.
PMID
8744579
Source
scival
Published In
AIDS Research and Human Retroviruses
Volume
12
Issue
8
Publish Date
1996
Start Page
683
End Page
693

Cytolytic responses elicited in phase I vaccine trials: The AVEG experience

Authors
Weinhold, KJ
MLA Citation
Weinhold, KJ. "Cytolytic responses elicited in phase I vaccine trials: The AVEG experience." 1996.
Source
wos-lite
Published In
RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES
Publish Date
1996
Start Page
261
End Page
267

Oligoclonal CD8 lymphocytes from persons with asymptomatic human immunodeficiency virus (HIV) type 1 infection inhibit HIV-1 replication.

CD8 lymphocytes from asymptomatic human immunodeficiency virus (HIV) type 1-infected patients can suppress virus production from infected CD4 cells. Suppressive activity is separate and distinct from cytotoxic T lymphocyte (CTL) reactivities and is likely mediated by a soluble factor(s). The majority of HIV-1 suppression studies have been done in the context of bulk CD8 cell cultures. In this study, viral suppression was characterized by clonal populations of CD8 cells derived from HIV-1-infected patients. Most of the suppressive clones were devoid of detectable CTL reactivity against env-, gag-, pol-, and nef-expressing targets. Among the suppressive clones derived from an individual patient, a marked heterogeneity was evident with respect to phenotypic markers, cytokine production, and T cell receptor V beta expression. These results suggest that noncytolytic virus suppression is oligoclonal in nature. Clones provide tools for future studies aimed at understanding the mechanism of suppression and identifying the suppressive factor.

Authors
Toso, JF; Chen, CH; Mohr, JR; Piglia, L; Oei, C; Ferrari, G; Greenberg, ML; Weinhold, KJ
MLA Citation
Toso, JF, Chen, CH, Mohr, JR, Piglia, L, Oei, C, Ferrari, G, Greenberg, ML, and Weinhold, KJ. "Oligoclonal CD8 lymphocytes from persons with asymptomatic human immunodeficiency virus (HIV) type 1 infection inhibit HIV-1 replication." J Infect Dis 172.4 (October 1995): 964-973.
PMID
7561217
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
172
Issue
4
Publish Date
1995
Start Page
964
End Page
973

IL-7 enhancement of antigen-driven activation/expansion of HIV-1-specific cytotoxic T lymphocyte precursors (CTLp).

CD8+ cytotoxic T lymphocytes are an important component in the immunologic control of human viral diseases. IL-7, a stromal cell-derived cytokine, has been demonstrated to enhance both anti-tumour and anti-viral CTL as well as lymphokine-activated killer (LAK) activity. We studied the ability of IL-7 to support the activation and the growth of in vitro antigen-specific CTL precursors (CTLp) present in peripheral blood mononuclear cells (PBMC) from HIV-infected patients. Results from these studies demonstrate that inclusion of IL-7 in a vaccinia/HIV-1 vector-based stimulation strategy greatly augmented overall CTL reactivities, whereas addition of IL-7 to unstimulated cultures failed to induce any significant anti-viral cytolytic activity. In four of six patients, HIV-specific lytic activities were significantly higher in cultures stimulated with antigen plus IL-7 compared with in vitro stimulation (IVS) with antigen alone. Cytotoxic activity was principally mediated by CD8+ effector cells, and CD3+/CD8+ cell expansion was increased by 2.7-fold in the presence of IL-7. In PBMC from seronegative donors, IL-7 enhanced anti-vaccinia CTL activities with less effect on cell proliferation. Furthermore, anti-gag CTL frequencies determined by limiting dilution analysis were increased by 2- and 10-fold in two asymptomatic patients following IVS plus IL-7 compared with antigen stimulation alone. Cytofluorimetric analysis revealed that IL-7 preferentially expanded CD8 memory cells (CD45RO+) and CD8+ lymphocytes expressing activation molecules. IL-7 was also able to support the growth of CD4+ lymphocytes, while having no effect on natural killer (NK)/K lymphocytes. Taken together, these data suggest that IL-7 acts cooperatively with the antigen supporting in vitro maturation of CTLp into functional cytotoxic effectors. Thus IL-7 may be an important biologic entity to consider as part of future immune-based therapies in which ex vivo expansion of antigen-driven CTL is an important determinant.

Authors
Ferrari, G; King, K; Rathbun, K; Place, CA; Packard, MV; Bartlett, JA; Bolognesi, DP; Weinhold, KJ
MLA Citation
Ferrari, G, King, K, Rathbun, K, Place, CA, Packard, MV, Bartlett, JA, Bolognesi, DP, and Weinhold, KJ. "IL-7 enhancement of antigen-driven activation/expansion of HIV-1-specific cytotoxic T lymphocyte precursors (CTLp)." Clin Exp Immunol 101.2 (August 1995): 239-248.
PMID
7544247
Source
pubmed
Published In
Clinical & Experimental Immunology
Volume
101
Issue
2
Publish Date
1995
Start Page
239
End Page
248

CD3 delta and epsilon gene expression in CD3-CD16+ natural killer cell clones derived from thymic precursors.

To better understand the maturational stages during T-cell development, we studied the expression of CD3 delta and CD3 epsilon genes, as well as the presence of TCR gene rearrangements, within CD3-CD16+ NK clones derived from thymic precursors in vitro. Northern blot analysis revealed that CD3-CD16+ clones derived from CD7+CD3-CD4-CD8- (TN) thymocytes expressed transcripts for the CD3 epsilon gene; however, no transcripts for the CD3 delta gene were detected. Importantly, both the CD3 epsilon and CD3 delta genes were expressed in TN thymocytes examined prior to cloning. A CD7+CD8+CD3-CD4- thymocyte population that makes up only 0.4% of the total thymocyte pool was also isolated from human thymus. We determined the maturation potential of this CD7+CD8+CD3-CD4- population by limiting dilution cloning and found that 67% of the clones generated in vitro had a CD3-CD16+CD8+ phenotype. In contrast to the NK clones derived from TN precursors, most CD3-CD16+ clones derived from CD7+CD8+CD3-CD4- thymocytes expressed transcripts for both CD3 epsilon and CD3 delta genes. Southern blot analysis of the NK clones derived from either thymic precursor population revealed no rearrangement of the TCR beta or gamma genes. These results demonstrate that the TN progenitor population and their CD3-CD16+ progeny differ in their expression of the CD3 delta transcript and during in vitro culture there is loss of CD3 delta expression and acquisition of surface CD16 within these NK clones. Furthermore, the CD3-CD16+ clones derived from TN versus CD7+CD8+CD3-CD4- thymocytes differed in their expression of the CD3 delta gene. The signaling events regulating the expression of the CD3 invariant chain genes within immature lymphoid progenitor cells may be important in determining their eventual maturation into T-cell and NK-cell lineages in vivo.

Authors
DeNofrio, D; Radcliff, G; Weinhold, KJ; Denning, SM
MLA Citation
DeNofrio, D, Radcliff, G, Weinhold, KJ, and Denning, SM. "CD3 delta and epsilon gene expression in CD3-CD16+ natural killer cell clones derived from thymic precursors." Hum Immunol 43.4 (August 1995): 283-294.
PMID
7499176
Source
pubmed
Published In
Human Immunology
Volume
43
Issue
4
Publish Date
1995
Start Page
283
End Page
294

Induction of human immunodeficiency virus type 1 (HIV-1)-specific cytolytic T lymphocyte responses in seronegative adults by a nonreplicating, host-range-restricted canarypox vector (ALVAC) carrying the HIV-1MN env gene.

CD8+ cytolytic T lymphocytes (CTL) are likely to be an important component of effective vaccines against human immunodeficiency virus type 1 (HIV-1). CTL can be induced most effectively with live virus vectors. However, because of concerns about the safety of such vectors, a nonreplicating canarypox vector (ALVAC) capable of expressing foreign genes in mammalian cells has been developed. This study evaluated the capacity of an ALVAC vector expressing the HIV-1MN envelope (env) glycoprotein to induce HIV-1-specific CTL in seronegative volunteers. Protocols were designed to determine whether immunization with ALVAC alone or in combination with subunit boosting could induce CTL in vaccinia-immune and -naive volunteers. A simple method for antigen-specific in vitro stimulation was used to detect CTL responses in HIV-1-seronegative vaccine recipients. The results indicate that low doses of a nonreplicating virus vector alone can elicit both CD4+ and CD8+ HIV-1-specific CTL in a subset of seronegative volunteers.

Authors
Egan, MA; Pavlat, WA; Tartaglia, J; Paoletti, E; Weinhold, KJ; Clements, ML; Siliciano, RF
MLA Citation
Egan, MA, Pavlat, WA, Tartaglia, J, Paoletti, E, Weinhold, KJ, Clements, ML, and Siliciano, RF. "Induction of human immunodeficiency virus type 1 (HIV-1)-specific cytolytic T lymphocyte responses in seronegative adults by a nonreplicating, host-range-restricted canarypox vector (ALVAC) carrying the HIV-1MN env gene." J Infect Dis 171.6 (June 1995): 1623-1627.
PMID
7769304
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
171
Issue
6
Publish Date
1995
Start Page
1623
End Page
1627

Multiple CTL specificities against autologous HIV-1-infected BLCLs.

The cellular immune response to HIV-1 has been well studied but, in many respects, remains incompletely defined. Although CTL specificities against highly conserved HIV-1 determinants as dictated by vaccinia/HIV-1 vector constructs have been described, much less is known regarding patient cellular reactivities against autologous cells infected with HIV-1. One of the main obstacles in characterizing this cellular reactivity has been the absence of a targeting system which accurately represents the HIV infected cell in vivo and is, at the same time, adaptable for in vitro assays. Through the use of two separate strategies aimed at increasing cellular CD4 expression, we were able to infect B-lymphocyte cell lines (BLCLs) with multiple strains of HIV-1. HIV-1-infected BLCLs were recognized by autologous effector cells with cytolytic specificities against env, gag, or pol determinants. In addition, HIV-1-infected BLCLs were capable of eliciting in vitro CTL reactivities directed against env-, gag-, and pol-expressing targets. This cellular reactivity was mediated by CD8+ cells and was MHC Class I restricted, suggesting a classical CTL response. Since multiple antigens are recognized, an HIV-1-infected BLCL is a more natural representation of an in vivo cellular target than other available testing systems and should permit a more representative analysis of CTL responses during infection or following vaccination.

Authors
Ahearne, PM; Morgan, RA; Sebastian, MW; Bolognesi, DP; Weinhold, KJ
MLA Citation
Ahearne, PM, Morgan, RA, Sebastian, MW, Bolognesi, DP, and Weinhold, KJ. "Multiple CTL specificities against autologous HIV-1-infected BLCLs." Cell Immunol 161.1 (March 1995): 34-41.
PMID
7867083
Source
pubmed
Published In
Cellular Immunology
Volume
161
Issue
1
Publish Date
1995
Start Page
34
End Page
41
DOI
10.1006/cimm.1995.1006

Vaccine-induced protection of chimpanzees against infection by a heterologous human immunodeficiency virus type 1

The extraordinary genetic diversity of human immunodeficiency virus type 1 (HIV-1) is a major problem to overcome in the development of an effective vaccine. In the most reliable animal model of HIV-1 infection, chimpanzees were immunized with various combinations of HIV-1 antigens, which were derived primarily from the surface glycoprotein, gp160, of HIV-1 strains LAI and MN. The immunogens also included a live recombinant canarypox virus expressing a gp160-MN protein. In one experiment, two chimpanzees were immunized multiple times; one animal received antigens derived only from HIV- 1(LAI), and the second animal received antigens from both HIV-1(LAI) and HIV- 1(MN). In another experiment, four chimpanzees were immunized in parallel a total of five times over 18 months; two animals received purified gp160 and V3-MN peptides, whereas the other two animals received the recombinant canarypox virus and gp160. At 3 months after the final booster, all immunized and naive control chimpanzees were challenged by intravenous inoculation of HIV-1(SF2); therefore, the study represented an intrasubtype B heterologous virus challenge. Virologic and serologic follow-up showed that the controls and the two chimpanzees immunized with the live recombinant canarypox virus became infected, whereas the other animals that were immunized with gp160 and V3-MN peptides were protected from infection. Evaluation of both cellular and humoral HIV-specific immune responses at the time of infectious HIV-1 challenge identified the following as possible correlates of protection: antibody titers to the V3 loop of MN and neutralizing antibody titers to HIV- 1(MN) or HIV-1(LAI), but not to HIV-1(SF2). The results of this study indicate that vaccine-mediated protection against intravenous infection with heterologous HIV-1 strains of the same subtype is possible with some immunogens.

Authors
Girard, M; Meignier, B; Barre-Sinoussi, F; Kieny, M-P; Matthews, T; Muchmore, E; Nara, PL; Wei, Q; Rimsky, L; Weinhold, K; Fultz, PN
MLA Citation
Girard, M, Meignier, B, Barre-Sinoussi, F, Kieny, M-P, Matthews, T, Muchmore, E, Nara, PL, Wei, Q, Rimsky, L, Weinhold, K, and Fultz, PN. "Vaccine-induced protection of chimpanzees against infection by a heterologous human immunodeficiency virus type 1." Journal of Virology 69.10 (1995): 6239-6248.
PMID
7666524
Source
scival
Published In
Journal of Virology
Volume
69
Issue
10
Publish Date
1995
Start Page
6239
End Page
6248

HIV-1 SPECIFIC CTL RESPONSES AMONG RECIPIENTS OF CANDIDATE AIDS VACCINES

Authors
WEINHOLD, KJ
MLA Citation
WEINHOLD, KJ. "HIV-1 SPECIFIC CTL RESPONSES AMONG RECIPIENTS OF CANDIDATE AIDS VACCINES." 1995.
Source
wos-lite
Published In
AIDS Research and Human Retroviruses
Volume
11
Publish Date
1995
Start Page
S130
End Page
S130

A novel method for detection and ex vivo expansion of HIV type 1-specific cytolytic T lymphocytes.

Studies have shown that cytolytic T lymphocyte (CTL) responses may be critical to the clearance of the early viremia in acute HIV-1 infection. It is likely that these cells play an important role in prolonging the asymptomatic phase of the infection. Although HIV-1-specific CTL activity can be detected in direct assays of freshly isolated peripheral blood lymphocytes (PBL) from some infected individuals, this method fails to detect CTL that are present at low frequency and resting, memory CTL. For these reasons, direct CTL assays on PBL from seropositive individuals may underestimate the level of CTL immunity. As part of ongoing investigations of CTL activity in HIV-1-infected individuals, we developed a novel strategy for the detection and ex vivo expansion of HIV-1-specific CTL. This technique involves selective stimulation of PBL from seropositive individuals with autologous Epstein-Barr virus (EBV)-transformed, B-lymphoblastoid cell lines (B-LCL) infected with vaccinia vectors expressing various HIV-1 genes. Prior to their use for in vitro stimulation, B-LCL are treated with psoralen and UV light to inactivate vaccinia virus. After 1 week of stimulation, CTL activity in stimulated cultures is measured in a standard 51Cr release assay. This ex vivo expansion method can selectively increase the bulk culture CTL activity against env, gag and nef, even in some seropositive individuals with low CD4 counts and little evidence of HIV-1-specific CTL in assays of freshly isolated PBL. These expanded CTL are predominantly of the CD8+ phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Lubaki, MN; Egan, MA; Siliciano, RF; Weinhold, KJ; Bollinger, RC
MLA Citation
Lubaki, MN, Egan, MA, Siliciano, RF, Weinhold, KJ, and Bollinger, RC. "A novel method for detection and ex vivo expansion of HIV type 1-specific cytolytic T lymphocytes." AIDS Res Hum Retroviruses 10.11 (November 1994): 1427-1431.
PMID
7888197
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
10
Issue
11
Publish Date
1994
Start Page
1427
End Page
1431
DOI
10.1089/aid.1994.10.1427

CD8+T-LYMPHOCYTE-MEDIATED INHIBITION OF HIV-1 LTR TRANSCRIPTION

Authors
CHEN, CH; WEINHOLD, KJ; BARTLETT, JA; BOLOGNESI, DP; GREENBERG, ML
MLA Citation
CHEN, CH, WEINHOLD, KJ, BARTLETT, JA, BOLOGNESI, DP, and GREENBERG, ML. "CD8+T-LYMPHOCYTE-MEDIATED INHIBITION OF HIV-1 LTR TRANSCRIPTION." August 1994.
Source
wos-lite
Published In
AIDS Research and Human Retroviruses
Volume
10
Publish Date
1994
Start Page
S36
End Page
S36

Delayed-Type Hypersensitivity Skin Tests Are an Independent Predictor of Human Immunodeficiency Virus Disease Progression

Authors
Gordin, FM; Hartigan, PM; Klimas, NG; Pazner, SBZ; Simberkoff, MS; Hamilton, AJD
MLA Citation
Gordin, FM, Hartigan, PM, Klimas, NG, Pazner, SBZ, Simberkoff, MS, and Hamilton, AJD. "Delayed-Type Hypersensitivity Skin Tests Are an Independent Predictor of Human Immunodeficiency Virus Disease Progression." Journal of Infectious Diseases 169.4 (April 1, 1994): 893-897.
Source
crossref
Published In
Journal of Infectious Diseases
Volume
169
Issue
4
Publish Date
1994
Start Page
893
End Page
897
DOI
10.1093/infdis/169.4.893

Comparison of anti-HIV-1 ADCC reactivities in infected humans and chimpanzees.

Despite its shortcomings as a disease model, the chimpanzee is still the most relevant animal model for human immunodeficiency virus type 1 (HIV-1) infection. Previous studies have revealed qualitative differences between human and chimpanzee anti-HIV-1 responses. In this study, the development of specific anti-HIV-1 antibody-dependent cellular cytotoxic (ADCC) reactivities was evaluated in chronically infected chimpanzees and compared to the human response, because anti-HIV-1 ADCC represents a major component of anti-envelope cytolytic response found in infected patients. Ten HIV-1-infected chimpanzees up to 5 years after the infection were investigated. Anti-HIV-1 ADCC-directing antibodies were detectable in only three of 10 infected chimpanzees, and in these animals, activity was apparent only several months after the HIV infection. In some of the infected animals, ADCC reactivity against infected cells preceded reactivity against gp120-coated targets. When anti-gp120 ADCC-directing antibodies were apparent, they exhibited the same broad reactivity described in humans against different HIV isolates. The pattern of ADCC reactivities in infected chimpanzees is completely different from the well-characterized anti-gp120 cytotoxic reactivities present in HIV-1-infected patients. It is a relatively rare and late-occurring event that may have an important bearing on the lack of virus-induced pathogenesis in the chimpanzee model.

Authors
Ferrari, G; Place, CA; Ahearne, PM; Nigida, SM; Arthur, LO; Bolognesi, DP; Weinhold, KJ
MLA Citation
Ferrari, G, Place, CA, Ahearne, PM, Nigida, SM, Arthur, LO, Bolognesi, DP, and Weinhold, KJ. "Comparison of anti-HIV-1 ADCC reactivities in infected humans and chimpanzees." J Acquir Immune Defic Syndr 7.4 (April 1994): 325-331.
PMID
8133445
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
7
Issue
4
Publish Date
1994
Start Page
325
End Page
331

Neutralizing antibodies to HIV-1 in seronegative volunteers immunized with recombinant gp120 from the MN strain of HIV-1

Objective. - To evaluate the safety and immunogenicity of the MN strain of recombinant gp120 (MN rgp120) as a vaccine prototype to prevent human immunodeficiency virus (HIV). Design. - Double-blind, randomized, placebo- controlled study with subjects vaccinated at 0, 4, 24, and 48 weeks and followed up through 64 weeks. Setting. - The AIDS Vaccine Evaluation Units in St Louis, Mo, Nashville, Tenn, and Rochester, NY, conducted the clinical study. Laboratory studies were conducted at Duke University, Raleigh, NC; data analysis was done by the Data Coordinating and Analysis Center at the EMMES Corporation, Potomac, Md. Participants. - Fifty-seven persons seronegative for HIV, at low risk for acquiring HIV infection, and 18 to 60 years of age. Interventions. - The MN rgp120 vaccine was administered to 12 volunteers each in doses of 100 μg, 300 μg, or 600 μg, and 12 volunteers received a combination of 300 μg of MN rgp120 vaccine and 300 μg of vaccine from rgp120 of strain IIIB. Nine volunteers received alum adjuvant alone (control). Main Outcome Measures. - Safety was assessed by monitoring lymphocyte subsets, serum creatinine, and liver enzymes. Immunogenicity was measured by enzyme-linked immunosorbent assay using the immunogen and synthetic peptide corresponding to the variable region 3 domain of gp120. Functional antibody assays included CD4 binding blocking; antibody-dependent, cell-mediated cytotoxicity; and neutralization of homologous and heterologous HIV strains. Results. - No severe adverse reactions occurred. In 33 of 48 volunteers, two doses of vaccine induced antibodies that neutralized the homologous strain HIV-1/MN. Three doses of vaccine induced antibodies that neutralized MN (in 46 of 48 volunteers), SF-2 (in 45 of 48 volunteers), or IIIB strains of HIV-1 (in 30 of 48 volunteers). Conclusion. - The vaccines were safe and immunogenic. Multiple injections of vaccine broadened and increased the neutralizing antibody response.

Authors
Belshe, RB; Graham, BS; Keefer, MC; Gorse, GJ; Wright, P; Dolin, R; Matthews, T; Weinhold, K; Bolognesi, DP; Sposto, R; Stablein, DM; Twaddell, T; Berman, PW; Gregory, T; Izu, AE; Walker, MC; Fast, P
MLA Citation
Belshe, RB, Graham, BS, Keefer, MC, Gorse, GJ, Wright, P, Dolin, R, Matthews, T, Weinhold, K, Bolognesi, DP, Sposto, R, Stablein, DM, Twaddell, T, Berman, PW, Gregory, T, Izu, AE, Walker, MC, and Fast, P. "Neutralizing antibodies to HIV-1 in seronegative volunteers immunized with recombinant gp120 from the MN strain of HIV-1." Journal of the American Medical Association 272.6 (1994): 475-480.
PMID
7913731
Source
scival
Published In
JAMA : the journal of the American Medical Association
Volume
272
Issue
6
Publish Date
1994
Start Page
475
End Page
480
DOI
10.1001/jama.272.6.475

Absence of recoverable infectious virus and unique immune responses in an asymptomatic HIV+ long-term survivor

We have studied a woman with transfusion-acquired HIV who appears to have contained infectious virus to consistently undetectable levels over a 13- year period without antiviral treatment. She received the infected transfusion for intra- and postpartum blood loss immediately after delivery of her second child in 1981. She had no acute febrile syndrome and has never had HIV-associated clinical signs or symptoms in the 13 years since infection. She was first tested and found positive for HIV antibodies in 1985, and the infected blood donor was diagnosed with AIDS in 1986 and died of AIDS-related complications in 1989. Two other recipients of packed erythrocytes from this donor (in 1980 and 1982) also became infected and were subsequently diagnosed with AIDS. Between January 1986 and April 1994, in the setting of continuous and unambiguous Western blot HIV-specific antibodies and intermittently positive low-level HIV DNA signal after polymerase chain reaction (PCR) amplification, more than 30 separate cell cocultures performed in several independent laboratories failed to yield evidence of infectious virus, despite special efforts to induce and detect HIV replication. Immunologically, a strong in vitro proliferative response to HIV envelope proteins also distinguished this subject from other asymptomatic HIV+ individuals.

Authors
Schwartz, D; Sharma, U; Busch, M; Weinhold, K; Matthews, T; Lieberman, J; Birx, D; Farzedagen, H; Margolick, J; Quinn, T; Davis, B; Bagasra, O; Pomerantz, R; Viscidi, R
MLA Citation
Schwartz, D, Sharma, U, Busch, M, Weinhold, K, Matthews, T, Lieberman, J, Birx, D, Farzedagen, H, Margolick, J, Quinn, T, Davis, B, Bagasra, O, Pomerantz, R, and Viscidi, R. "Absence of recoverable infectious virus and unique immune responses in an asymptomatic HIV+ long-term survivor." AIDS Research and Human Retroviruses 10.12 (1994): 1703-1711.
PMID
7888230
Source
scival
Published In
AIDS Research and Human Retroviruses
Volume
10
Issue
12
Publish Date
1994
Start Page
1703
End Page
1711

Conference on advances in AIDS vaccine development - 1993 summary: Correlates of HIV immunity working group

Authors
Sheppard, H; Bridges, SH; Mathieson, BJ; Walker, MC; Weinhold, K
MLA Citation
Sheppard, H, Bridges, SH, Mathieson, BJ, Walker, MC, and Weinhold, K. "Conference on advances in AIDS vaccine development - 1993 summary: Correlates of HIV immunity working group." AIDS Research and Human Retroviruses 10.SUPPL. 2 (1994): S171-S176.
PMID
7865294
Source
scival
Published In
AIDS Research and Human Retroviruses
Volume
10
Issue
SUPPL. 2
Publish Date
1994
Start Page
S171
End Page
S176

THE EFFECT OF INTERLEUKIN-7 ON FUNCTIONAL AND PHENOTYPIC PROPERTIES OF ANTIGEN-DRIVEN CTL

Authors
FERRARI, G; KING, K; PACKARD, M; BARTLETT, JA; TARTAGLIA, J; TOSO, J; WEINHOLD, KJ
MLA Citation
FERRARI, G, KING, K, PACKARD, M, BARTLETT, JA, TARTAGLIA, J, TOSO, J, and WEINHOLD, KJ. "THE EFFECT OF INTERLEUKIN-7 ON FUNCTIONAL AND PHENOTYPIC PROPERTIES OF ANTIGEN-DRIVEN CTL." 1994.
Source
wos-lite
Published In
Journal of Cellular Biochemistry
Publish Date
1994
Start Page
354
End Page
354

CYTOTOXIC T-LYMPHOCYTE REACTIVITIES AMONG HIV-1 VACCINE RECIPIENTS IN THE AIDS VACCINE EVALUATION NETWORK

Authors
WEINHOLD, KJ; RATHBUN, KT; PLACE, CA; FERRARI, G; BOLOGNESI, DP
MLA Citation
WEINHOLD, KJ, RATHBUN, KT, PLACE, CA, FERRARI, G, and BOLOGNESI, DP. "CYTOTOXIC T-LYMPHOCYTE REACTIVITIES AMONG HIV-1 VACCINE RECIPIENTS IN THE AIDS VACCINE EVALUATION NETWORK." 1994.
Source
wos-lite
Published In
AIDS Research and Human Retroviruses
Volume
10
Publish Date
1994
Start Page
S89
End Page
S89

CD8+ T lymphocyte-mediated inhibition of HIV-1 long terminal repeat transcription: a novel antiviral mechanism.

HIV-1 infection evokes a vigorous antiviral response that may participate in resolving the initial peak of plasma viremia and maintenance of the asymptomatic state. CD8+ T lymphocytes of HIV-1-infected individuals play a critical role in the cellular anti-HIV response. In agreement with previous reports, we observed a potent suppressive effect on HIV-1 production from autologous CD4+ T lymphocytes by CD8+ T lymphocytes from asymptomatic HIV-1-infected individuals. To elucidate the mechanism(s) of the nonlytic suppressive antiviral activity, we examined the effect of CD8+ T lymphocytes on the transcriptional activity of the HIV-1 promoter (HIV-LTR). CD8+ lymphocytes from HIV-1-infected asymptomatic individuals suppressed tat-mediated HIV-LTR transcription in CD4+ lymphocytes. HIV-LTR transcriptional activity was suppressed by CD8 lymphocytes to an extent similar to tat-mediated transcription whereas CMV immediate early gene promoter activity was not affected. In contrast to the suppressive effect seen with CD8+ lymphocytes from HIV-1-infected individuals, CD8+ lymphocytes from uninfected individuals did not significantly inhibit tat-mediated or HIV-LTR transcription. The transcriptional inhibitory activity was not MHC class I restricted and could be mediated by a soluble factor(s). Supernatants from some CD8+ T lymphocyte cultures from HIV-1+ individuals exerted an inhibitory effect on tat-mediated HIV-LTR transcription comparable to that seen with CD8+ cells. In conclusion, CD8+ lymphocytes from asymptomatic HIV-1+ individuals could suppress virus production by inhibiting HIV-1 gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Chen, CH; Weinhold, KJ; Bartlett, JA; Bolognesi, DP; Greenberg, ML
MLA Citation
Chen, CH, Weinhold, KJ, Bartlett, JA, Bolognesi, DP, and Greenberg, ML. "CD8+ T lymphocyte-mediated inhibition of HIV-1 long terminal repeat transcription: a novel antiviral mechanism." AIDS Res Hum Retroviruses 9.11 (November 1993): 1079-1086.
PMID
8312050
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
9
Issue
11
Publish Date
1993
Start Page
1079
End Page
1086
DOI
10.1089/aid.1993.9.1079

The impact of HIV-1 infection on phenotypic and functional parameters of cellular immunity in chimpanzees.

As a means of assessing the immunological impact of HIV infection in the chimpanzee, as well as the participation of the cellular components in the control of HIV infection in these animals, various aspects of cellular immunity were investigated in chronically HIV-infected chimpanzees. Eight HIV-1-infected chimpanzees were included in this study; two of them were infected for more than 5 years and six for nearly 3 years at the time of study. All of the chimpanzees received either 40 or 100 TCID50 of HTLV-IIIB. Circulating peripheral blood lymphocytes were studied by flow cytofluorimetric analysis in order to reveal possible alterations in the CD4:CD8 ratio, as well as in specific CD4+ and CD8+ cell subpopulations. Chronically infected chimpanzees did not present significant alterations in the percentage of CD4+ or CD8+ lymphocyte subsets. Interestingly, the CD8+/CD57+ cell subset was not detectable. The expression of markers for activation on circulating lymphocytes, usually higher in the HIV-infected patients, was not altered in infected animals. The functional aspects of specific anti-HIV-1 non-MHC and MHC-restricted cellular cytotoxic reactivities were also investigated. The results were compared with the findings in normal uninfected chimpanzees and in HIV-infected humans. Only one chimpanzee (881) developed a detectable, specific non-MHC-restricted anti-HIV-1- reactivity. Compared to that seen in humans, the ontogeny of this activity is delayed. Among the other infected chimpanzees, no specific anti-HIV cellular reactivities were detectable in the peripheral blood. In chimpanzees, HIV-1 infection evidently does not elicit the same strong cellular reactivity as that detected in infected patients. The absence of chronic cellular activation, despite continued viral replication, may highlight a key determinant in HIV-1-induced pathogenesis that is likewise absent in infected chimpanzees.

Authors
Ferrari, G; Ottinger, J; Place, C; Nigida, SM; Arthur, LO; Weinhold, KJ
MLA Citation
Ferrari, G, Ottinger, J, Place, C, Nigida, SM, Arthur, LO, and Weinhold, KJ. "The impact of HIV-1 infection on phenotypic and functional parameters of cellular immunity in chimpanzees." AIDS Res Hum Retroviruses 9.7 (July 1993): 647-656.
PMID
8369169
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
9
Issue
7
Publish Date
1993
Start Page
647
End Page
656
DOI
10.1089/aid.1993.9.647

CD8+ T-LYMPHOCYTES FROM ASYMPTOMATIC HIV-1 INFECTED INDIVIDUALS SUPPRESS TAT-MEDIATED HIV-1 LTR TRANSCRIPTION

Authors
CHEN, CH; WEINHOLD, KJ; BARTLETT, JA; MACDOUGALL, MJ; GREENBERG, ML
MLA Citation
CHEN, CH, WEINHOLD, KJ, BARTLETT, JA, MACDOUGALL, MJ, and GREENBERG, ML. "CD8+ T-LYMPHOCYTES FROM ASYMPTOMATIC HIV-1 INFECTED INDIVIDUALS SUPPRESS TAT-MEDIATED HIV-1 LTR TRANSCRIPTION." March 29, 1993.
Source
wos-lite
Published In
Journal of Cellular Biochemistry
Publish Date
1993
Start Page
75
End Page
75

TH1 AND TH2 CD4 SUBSET RESPONSES IN HIV-1 INFECTED INDIVIDUALS AT VARIOUS STAGES OF DISEASE

Authors
FERRARI, G; PACKARD, MV; BARTLETT, JA; WEINHOLD, KJ
MLA Citation
FERRARI, G, PACKARD, MV, BARTLETT, JA, and WEINHOLD, KJ. "TH1 AND TH2 CD4 SUBSET RESPONSES IN HIV-1 INFECTED INDIVIDUALS AT VARIOUS STAGES OF DISEASE." March 29, 1993.
Source
wos-lite
Published In
Journal of Cellular Biochemistry
Publish Date
1993
Start Page
78
End Page
78

Conversion of an immunogenic human immunodeficiency virus (HIV) envelope synthetic peptide to a tolerogen in chimpanzees by the fusogenic domain of HIV gp41 envelope protein.

The fusogenic (F) domain of human immunodeficiency virus (HIV) gp41 envelope (env) protein has sequence similarities to many virus and mediates the fusion of HIV-infected cells. During a survey of the immunogenicity of HIV env peptides in chimpanzees, we have observed that HIV peptide immunogenicity was dramatically altered by the NH2-terminal synthesis of the gp41 F domain to an otherwise immunogenic peptide. We compared two hybrid peptide types comprised of T helper (Th) and B cell epitopes of HIV gp120 env protein for their immunogenicity in chimpanzees. The Th-B epitope hybrid peptides contained the HIV gp120 Th cell determinant, T1 (amino acids [aa] 428-440)-synthesized NH2 terminal to gp120 V3 loop peptides, which contain B cell epitopes that induce anti-HIV-neutralizing antibodies (SP10IIIB [aa 303-321] and SP10IIIB [A] [aa 303-327]). The F-Th-B peptide contained the HIV gp41 F domain of HIVIIIB gp41 (aa 519-530)-synthesized NH2 terminal to the Th-B peptide. Whereas Th-B peptides were potent immunogens for chimpanzee antibody and T cell-proliferative responses, the F-Th-B peptide induced lower anti-HIV gp120 T and B cell responses. Moreover, immunization of chimpanzees with F-Th-B peptide but not Th-B peptides induced a significant decrease in peripheral blood T lymphocytes (mean decrease during immunization, 52%; p < 0.02). Chimpanzees previously immunized with F-Th-B peptide did not respond well to immunization with Th-B peptide with T or B cell responses to HIV peptides, demonstrating that the F-Th-B peptide induced immune hyporesponsiveness to Th and B HIV gp120 env determinants. These observations raise the hypothesis that the HIV gp41 env F domain may be a biologically active immunoregulatory peptide in vivo, and by an as yet uncharacterized mechanism, promotes primate immune system hyporesponsiveness to otherwise immunogenic peptides.

Authors
Haynes, BF; Arthur, LO; Frost, P; Matthews, TJ; Langlois, AJ; Palker, TJ; Hart, MK; Scearce, RM; Jones, DM; McDanal, C
MLA Citation
Haynes, BF, Arthur, LO, Frost, P, Matthews, TJ, Langlois, AJ, Palker, TJ, Hart, MK, Scearce, RM, Jones, DM, and McDanal, C. "Conversion of an immunogenic human immunodeficiency virus (HIV) envelope synthetic peptide to a tolerogen in chimpanzees by the fusogenic domain of HIV gp41 envelope protein." J Exp Med 177.3 (March 1, 1993): 717-727.
PMID
7679708
Source
pubmed
Published In
The Journal of Experimental Medicine
Volume
177
Issue
3
Publish Date
1993
Start Page
717
End Page
727

Enhanced p24 antigen detection in sera from human immunodeficiency virus-infected children.

Authors
Walter, EB; Weinhold, KJ; Wilfert, CM
MLA Citation
Walter, EB, Weinhold, KJ, and Wilfert, CM. "Enhanced p24 antigen detection in sera from human immunodeficiency virus-infected children." Pediatr Infect Dis J 12.1 (January 1993): 94-96.
PMID
8417433
Source
pubmed
Published In
Pediatric Infectious Disease Journal
Volume
12
Issue
1
Publish Date
1993
Start Page
94
End Page
96

Detection of anti-human cell antibodies in sera from macaques immunized with whole inactivated virus.

More than 200 sera from macaques immunized with several different vaccine preparations were tested in various assays with cells of human and macaque origin. Only in instances where whole inactivated SIV preparations were used for immunization, were reactivities found with normal human cells, and this was the case in every instance. Such sera produced a marked clumping of several normal human cell lines and exhibited strong staining of the cell surface in FACS analysis. In the presence of SIVDeltaB670, these sera also enhanced infectivity and fusion formation. When similar tests were performed with macaque cells as targets, such phenomena were not easily discernible. Likewise, there was no trace of such activities in sera from normal animals, animals chronically infected with SIV, or in those from animals which received recombinant viral subunits as vaccines. Finally, we show that in several instances where whole inactivated virus was used as a vaccine, there is a strong correlation between the titer of anticellular activity with protection.

Authors
Langlois, AJ; Weinhold, KJ; Matthews, TJ; Greenberg, ML; Bolognesi, DP
MLA Citation
Langlois, AJ, Weinhold, KJ, Matthews, TJ, Greenberg, ML, and Bolognesi, DP. "Detection of anti-human cell antibodies in sera from macaques immunized with whole inactivated virus." AIDS Res Hum Retroviruses 8.9 (September 1992): 1641-1652.
PMID
1457210
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
8
Issue
9
Publish Date
1992
Start Page
1641
End Page
1652
DOI
10.1089/aid.1992.8.1641

Specific activation strategies for amplification of low CTL signals.

Authors
Weinhold, KJ; Tartaglia, J; Paoletti, E; Graham, B; Schwartz, D; McElrath, J; Roberts, N; Gorse, G
MLA Citation
Weinhold, KJ, Tartaglia, J, Paoletti, E, Graham, B, Schwartz, D, McElrath, J, Roberts, N, and Gorse, G. "Specific activation strategies for amplification of low CTL signals." AIDS Res Hum Retroviruses 8.8 (August 1992): 1373-.
PMID
1466958
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
8
Issue
8
Publish Date
1992
Start Page
1373
DOI
10.1089/aid.1992.8.1373

COMPARISON OF CELLULAR ANTIVIRAL CYTOTOXICITIES PRESENT IN HIV-1 INFECTED HUMANS AND CHIMPANZEES

Authors
WEINHOLD, KJ; FERRARI, G; ARTHUR, LO
MLA Citation
WEINHOLD, KJ, FERRARI, G, and ARTHUR, LO. "COMPARISON OF CELLULAR ANTIVIRAL CYTOTOXICITIES PRESENT IN HIV-1 INFECTED HUMANS AND CHIMPANZEES." May 1992.
Source
wos-lite
Published In
AIDS Research and Human Retroviruses
Volume
8
Issue
5
Publish Date
1992
Start Page
938
End Page
938

A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection. Results of the Veterans Affairs Cooperative Study.

BACKGROUND: Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established. METHODS: We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed. RESULTS: During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen. Early therapy was associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas late therapy was associated with more skin rash. CONCLUSIONS: In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects.

Authors
Hamilton, JD; Hartigan, PM; Simberkoff, MS; Day, PL; Diamond, GR; Dickinson, GM; Drusano, GL; Egorin, MJ; George, WL; Gordin, FM
MLA Citation
Hamilton, JD, Hartigan, PM, Simberkoff, MS, Day, PL, Diamond, GR, Dickinson, GM, Drusano, GL, Egorin, MJ, George, WL, and Gordin, FM. "A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection. Results of the Veterans Affairs Cooperative Study." N Engl J Med 326.7 (February 13, 1992): 437-443.
PMID
1346337
Source
pubmed
Published In
The New England journal of medicine
Volume
326
Issue
7
Publish Date
1992
Start Page
437
End Page
443
DOI
10.1056/NEJM199202133260703

The ability of certain SIV vaccines to provoke reactions against normal cells.

Authors
Langlois, AJ; Weinhold, KJ; Matthews, TJ; Greenberg, ML; Bolognesi, DP
MLA Citation
Langlois, AJ, Weinhold, KJ, Matthews, TJ, Greenberg, ML, and Bolognesi, DP. "The ability of certain SIV vaccines to provoke reactions against normal cells." Science 255.5042 (January 17, 1992): 292-293.
PMID
1549775
Source
pubmed
Published In
Science
Volume
255
Issue
5042
Publish Date
1992
Start Page
292
End Page
293

CTL cross reactivity between HIV strains

Authors
Jolly, D; Chada, S; Townsend, K; DeJesus, C; Chang, S; Weinhold, K; Anderson-, CG; Lynn, A; Bodner, M; Barber, J; Warner, J
MLA Citation
Jolly, D, Chada, S, Townsend, K, DeJesus, C, Chang, S, Weinhold, K, Anderson-, CG, Lynn, A, Bodner, M, Barber, J, and Warner, J. "CTL cross reactivity between HIV strains." AIDS Research and Human Retroviruses 8.8 (1992): 1369-1371.
PMID
1466957
Source
scival
Published In
AIDS Research and Human Retroviruses
Volume
8
Issue
8
Publish Date
1992
Start Page
1369
End Page
1371

Priming of anti-human immunodeficiency virus (HIV) CD8+ cytotoxic T cells in vivo by carrier-free HIV synthetic peptides.

The generation of antiviral cytotoxic T lymphocytes (CTLs) is a critical component of the immune response to viral infections. A safe and nontoxic vaccine for AIDS would optimally use a carrier-free synthetic peptide immunogen containing only components of HIV necessary for induction of protective immune responses. We report that hybrid synthetic peptides containing either a HIV envelope gp120 T-cell determinant (T1) or the envelope gp41 fusion domain (F) N-terminal to HIV CTL determinants are capable of priming murine CD8+, major histocompatibility complex class I-restricted anti-HIV CTLs in vivo. These data demonstrate that carrier-free, nonderivatized synthetic peptides can be used in vivo to induce anti-HIV CTL responses.

Authors
Hart, MK; Weinhold, KJ; Scearce, RM; Washburn, EM; Clark, CA; Palker, TJ; Haynes, BF
MLA Citation
Hart, MK, Weinhold, KJ, Scearce, RM, Washburn, EM, Clark, CA, Palker, TJ, and Haynes, BF. "Priming of anti-human immunodeficiency virus (HIV) CD8+ cytotoxic T cells in vivo by carrier-free HIV synthetic peptides." Proc Natl Acad Sci U S A 88.21 (November 1, 1991): 9448-9452.
PMID
1946358
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
88
Issue
21
Publish Date
1991
Start Page
9448
End Page
9452

Analysis of clones derived from human CD7+CD4-CD8-CD3- thymocytes.

The differentiation of human thymocyte precursors was studied by analysis of clonal progeny of CD4-CD8-CD3- (triple negative or TN) thymocytes. Using a culture system of phytohemagglutinin, IL-2, and irradiated allogeneic lymphoid feeder cells, we found that 48% of clones (104 total) derived from TN thymocyte suspensions were TCR gamma delta cells, 12% of clones were TCR alpha beta cells, and 34% were CD16+CD3- cells. Importantly, 6% of clones were novel subsets of CD4+CD8-CD3- or CD4-CD8+CD3- thymocytes. The majority of TCR alpha beta, TCR gamma delta, and CD16+CD3- clones expressed low levels of CD4. Molecular analysis of freshly isolated TN- thymocytes prior to in vitro culture demonstrated that up to 40% of cells had TCR gamma, delta, and beta gene rearrangements, but were negative in indirect immunofluorescence assays for cytoplasmic TCR delta and beta. These data provide evidence at the clonal level for the presence of precursors of the TCR alpha beta and TCR gamma delta lineages in the human TN thymocyte pool. Moreover, a substantial proportion of freshly isolated human TN thymocytes had already undergone TCR gene rearrangement prior to in vitro culture. Whether these precursors of the TCR alpha beta and TCR gamma delta lineages mature from cells already containing TCR gene rearrangements into sTCR+ cells or differentiate in vitro from cells with TCR genes in germline configuration remains to be determined. Nonetheless, these data demonstrate that the predominant clone types that grow out of human TN thymocytes in vitro are TCR gamma delta and NK cells.

Authors
Denning, SM; Jones, DM; Ware, RE; Weinhold, KJ; Brenner, MB; Haynes, BF
MLA Citation
Denning, SM, Jones, DM, Ware, RE, Weinhold, KJ, Brenner, MB, and Haynes, BF. "Analysis of clones derived from human CD7+CD4-CD8-CD3- thymocytes." Int Immunol 3.10 (October 1991): 1015-1024.
PMID
1721831
Source
pubmed
Published In
International Immunology
Volume
3
Issue
10
Publish Date
1991
Start Page
1015
End Page
1024

Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant: further clarifications.

Authors
LaRosa, GJ; Weinhold, K; Profy, AT; Langlois, AJ; Dreesman, GR; Boswell, RN; Shadduck, P; Bolognesi, DP; Matthews, TJ; Emini, EA
MLA Citation
LaRosa, GJ, Weinhold, K, Profy, AT, Langlois, AJ, Dreesman, GR, Boswell, RN, Shadduck, P, Bolognesi, DP, Matthews, TJ, and Emini, EA. "Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant: further clarifications." Science 253.5024 (September 6, 1991): 1146-.
PMID
1887238
Source
pubmed
Published In
Science
Volume
253
Issue
5024
Publish Date
1991
Start Page
1146

The effect of AZT on in vitro lymphokine-activated killer (LAK) activity in human immunodeficiency virus type-1 (HIV-1) infected individuals.

Human immunodeficiency virus type-1 (HIV-1)-infected individuals exhibit functional impairment in various forms of cell-mediated cytotoxicities (CMC) at all stages of disease. The purpose of this study was to determine (i) if peripheral blood mononuclear cells (PBMC) obtained from HIV-1-infected patients could be stimulated in vitro to yield lymphokine-activated killer (LAK) activity; (ii) if non-MHC-restricted gp120-specific CMC could be preserved; and (iii) what effect zidovudine (AZT) would have on LAK activity. Fourteen asymptomatic HIV-1 seropositive adults and five healthy seronegative adults (controls) were evaluated. PBMCs were isolated and incubated in media or supplemented with IL-2 for 4 or 72 hr. Lysis of the NK resistant target cell line, Daudi, was similar for the control and experimental group. The increase in activity after stimulation was elevated to a similar degree in both seronegative and seropositive groups (P less than 0.001). LAK activity was significantly decreased (P = 0.011) when AZT was added to LAK cultures. In addition, virus production may not have been completely inhibited by AZT in LAK cultures. Thus, PBMCs from asymptomatic HIV-1-infected patients could be stimulated to yield LAK activity. However, AZT can impair LAK generation. It is unclear if LAK activation results in virus production that cannot be inhibited by AZT in this system. Further definition in other patient populations is required prior to applying this information to clinical trials.

Authors
Stine, KC; Tyler, DS; Stanley, SD; Bartlett, JA; Bolognesi, DP; Weinhold, KJ
MLA Citation
Stine, KC, Tyler, DS, Stanley, SD, Bartlett, JA, Bolognesi, DP, and Weinhold, KJ. "The effect of AZT on in vitro lymphokine-activated killer (LAK) activity in human immunodeficiency virus type-1 (HIV-1) infected individuals." Cell Immunol 136.1 (August 1991): 165-172.
PMID
1905587
Source
pubmed
Published In
Cellular Immunology
Volume
136
Issue
1
Publish Date
1991
Start Page
165
End Page
172

In vitro assays for detecting neutralizing and fusion-inhibiting antibodies to SIVMAC251.

Sensitive and reproducible assays for SIV infection and syncytium formation have been developed in which high titers of neutralizing and fusion-inhibiting antibodies can be recorded. These assays will contribute toward our understanding of the role of humoral responses in SIV vaccine strategies.

Authors
Langlois, AJ; Weinhold, KJ; Matthews, TJ; Bolognesi, DP
MLA Citation
Langlois, AJ, Weinhold, KJ, Matthews, TJ, and Bolognesi, DP. "In vitro assays for detecting neutralizing and fusion-inhibiting antibodies to SIVMAC251." AIDS Res Hum Retroviruses 7.8 (August 1991): 713-720.
PMID
1718347
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
7
Issue
8
Publish Date
1991
Start Page
713
End Page
720
DOI
10.1089/aid.1991.7.713

MONOCYTES FROM HIV-1 SEROPOSITIVE INDIVIDUALS HAVE NORMAL ANTI-CRYPTOCOCCAL ACTIVITY

Authors
CAMERON, ML; SEBASTIAN, MW; GRANGER, DL; MATTHEWS, TJ; WEINHOLD, KJ; WEINBERG, JB
MLA Citation
CAMERON, ML, SEBASTIAN, MW, GRANGER, DL, MATTHEWS, TJ, WEINHOLD, KJ, and WEINBERG, JB. "MONOCYTES FROM HIV-1 SEROPOSITIVE INDIVIDUALS HAVE NORMAL ANTI-CRYPTOCOCCAL ACTIVITY." April 1991.
Source
wos-lite
Published In
Clinical Research
Volume
39
Issue
2
Publish Date
1991
Start Page
A361
End Page
A361

HIV SYNTHETIC PEPTIDES CONTAINING T-CELL AND B-CELL EPITOPES INDUCE HIV-SPECIFIC CD8+ CYTOTOXIC T-CELL RESPONSES INVIVO

Authors
HART, MK; WEINHOLD, KJ; WASHBURN, E; SCEARCE, RM; CLARK, C; PALKER, TJ; HAYNES, BF
MLA Citation
HART, MK, WEINHOLD, KJ, WASHBURN, E, SCEARCE, RM, CLARK, C, PALKER, TJ, and HAYNES, BF. "HIV SYNTHETIC PEPTIDES CONTAINING T-CELL AND B-CELL EPITOPES INDUCE HIV-SPECIFIC CD8+ CYTOTOXIC T-CELL RESPONSES INVIVO." March 15, 1991.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
5
Issue
5
Publish Date
1991
Start Page
A1334
End Page
A1334

Preparation and characterization of an intravenous solution of IgG from human immunodeficiency virus-seropositive donors.

An intravenous solution of 99% pure globulin (hyperimmune IgG, HIVIG) was obtained from pooled plasma of selected human immunodeficiency virus (HIV-1)-seropositive asymptomatic donors with greater than 400 CD4+/microliters cells per microliter and a high titer of antibody to HIV-1 p24 protein. HIVIG had high titers of antibody to p24, glycoprotein 41 (gp41), and gp120, group-specific neutralizing activity, and binding to the gp120 hypervariable loop region. It inhibited syncytia formation. At low concentration, it enhanced viral production of HIV-1 in infected peripheral blood monocytes but was inhibitory at higher concentration. HIVIG directed group-specific antibody-dependent cellular cytotoxicity against HIV-infected targets. For a period of 6 to 28 months, plasma donors kept stable antibody titers and had a 1.0% decrease in CD4+ cells per month. One gram per kilogram HIVIG injected in two juvenile chimpanzees was well tolerated and did not transmit HIV, as measured by negative cell culture, IgM immune response to HIV proteins, and polymerase chain reaction. The mean half-life of HIV-1 p24 antibody was 15 days. These preliminary data suggest that HIVIG is a safe product suitable for clinical trial in HIV-1-infected individuals.

Authors
Cummins, LM; Weinhold, KJ; Matthews, TJ; Langlois, AJ; Perno, CF; Condie, RM; Allain, JP
MLA Citation
Cummins, LM, Weinhold, KJ, Matthews, TJ, Langlois, AJ, Perno, CF, Condie, RM, and Allain, JP. "Preparation and characterization of an intravenous solution of IgG from human immunodeficiency virus-seropositive donors." Blood 77.5 (March 1, 1991): 1111-1117.
PMID
1995097
Source
pubmed
Published In
Blood
Volume
77
Issue
5
Publish Date
1991
Start Page
1111
End Page
1117

Anti-HIV-1 ADCC: clinical and therapeutic implications.

The predominant antienvelope cell-mediated cytotoxicity in HIV-1-infected patients is a direct form of antibody-dependent cellular cytotoxicity (ADCC) in which circulating NK/K cells armed with cytophilic antibodies comprise a cytolytic effector cell complex capable of destroying HIV-1-expressing targets. This non-MHC-restricted form of virus-specific cytotoxicity is present in most infected patients, with maximum activity in early disease, gradually declining with disease progression. This endogenous cytotoxicity provides a focal point in the design of interventive strategies involving immune-based therapies. In the first such attempts, the lymphokine interleukin-2 has been employed in an effort to augment these potentially beneficial cytolytic reactivities. The focus of this article is to present the rationale, early clinical results, and future direction of such therapeutic approaches and, in doing so, to illustrate how careful basic research findings can be applied to the design of rational therapeutic strategies.

Authors
Weinhold, KJ
MLA Citation
Weinhold, KJ. "Anti-HIV-1 ADCC: clinical and therapeutic implications." Biotechnol Ther 2.1-2 (1991): 147-157. (Review)
PMID
1845118
Source
pubmed
Published In
Biotechnology therapeutics
Volume
2
Issue
1-2
Publish Date
1991
Start Page
147
End Page
157

Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant: Corrections and clarifications

Authors
LaRosa, GJ; Davide, JP; Weinhold, K; Waterbury, JA; Profy, AT; Lewis, JA; Langlois, AJ; Dreesman, GR; Boswell, RN; Shadduck, P; Holley, LH; Karplus, M; Bolognesi, DP; Matthews, TJ; Emini, EA; Putney, SD
MLA Citation
LaRosa, GJ, Davide, JP, Weinhold, K, Waterbury, JA, Profy, AT, Lewis, JA, Langlois, AJ, Dreesman, GR, Boswell, RN, Shadduck, P, Holley, LH, Karplus, M, Bolognesi, DP, Matthews, TJ, Emini, EA, and Putney, SD. "Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant: Corrections and clarifications." Science 251.4995 (1991): 811--.
PMID
1990444
Source
scival
Published In
Science
Volume
251
Issue
4995
Publish Date
1991
Start Page
811-

Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies.

In an effort to determine the functional activity of anti-HIV-1 human mAb and to define the epitopes against which they are directed, supernatants from 10 EBV-transformed lymphoblastoid cell lines producing mAb to HIV were tested. Five clones producing mAb to gp41 and five producing mAb to p24 were identified. The anti-HIV-1 human mAb were tested in neutralization and cell fusion assays in the form of cell culture supernatants at concentrations ranging from 1.7 to 22.0 micrograms/ml. None of the human mAb were found either to inhibit HIV-1-(IIIB or RF) associated cell fusion or to neutralize HIV-1 (IIIB) infection of AA5 cells. All human mAb were additionally tested in 6 h 51Cr release assays for their ability to direct HIV-1 specific antibody-dependent cellular cytotoxicity (ADCC). For ADCC assays, PBMC were isolated from healthy seronegative donors and used as effector cells. HIV-1 infected (IIIB, RF, and MN) CEM.NKR cells as well as CEM.NKR cells with purified gp120 adsorbed onto their surface served as targets. None of the anti-p24 mAb mediated ADCC. In contrast, three of the anti-gp41 mAb were able to direct a significant level of ADCC against each of the infected targets, but as expected, failed to lyse gp120 adsorbed cells. To define the specific epitopes against which the anti-gp41 mAb were directed, seven small peptides homologous to regions within the extracellular domain of gp41 were synthesized. Using RIA, two of the mAb could be mapped. The most effective ADCC-directing human mAb bound to a peptide comprising amino acids 644-663, whereas the least effective ADCC directing anti-gp41 human mAb bound to a region within the immunodominant portion of gp41 outlined by amino acids 579-604. Together, these results for the first time assign a functional activity to human mAb directed at specific regions within gp41 by demonstrating that areas within this molecule can serve as targets for ADCC.

Authors
Tyler, DS; Stanley, SD; Zolla-Pazner, S; Gorny, MK; Shadduck, PP; Langlois, AJ; Matthews, TJ; Bolognesi, DP; Palker, TJ; Weinhold, KJ
MLA Citation
Tyler, DS, Stanley, SD, Zolla-Pazner, S, Gorny, MK, Shadduck, PP, Langlois, AJ, Matthews, TJ, Bolognesi, DP, Palker, TJ, and Weinhold, KJ. "Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies." J Immunol 145.10 (November 15, 1990): 3276-3282.
PMID
1700004
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
145
Issue
10
Publish Date
1990
Start Page
3276
End Page
3282

EVALUATION OF V3 REGION BASED SYNTHETIC PEPTIDE INOCULA AS VACCINES FOR HIV-1 AND SIV

Authors
PALKER, TJ; HART, MK; MATTHEWS, TJ; LANGLOIS, AJ; WEINHOLD, KJ; BOLOGNESI, DP; HAYNES, BF
MLA Citation
PALKER, TJ, HART, MK, MATTHEWS, TJ, LANGLOIS, AJ, WEINHOLD, KJ, BOLOGNESI, DP, and HAYNES, BF. "EVALUATION OF V3 REGION BASED SYNTHETIC PEPTIDE INOCULA AS VACCINES FOR HIV-1 AND SIV." November 1990.
Source
wos-lite
Published In
AIDS Research and Human Retroviruses
Volume
6
Issue
11
Publish Date
1990
Start Page
1358
End Page
1358

HIV-1 neutralizing monoclonal antibodies induced by a synthetic peptide.

We have developed a series of murine monoclonal antibodies to a region of the 120 kD envelope glycoprotein (gp120) of human immunodeficiency virus type 1 (HIV-1). This region has previously been implicated as a site for virus neutralization by antisera raised to recombinant proteins and by antibodies made to full-length gp120 purified from virus. The antigen employed was a synthetic peptide containing 15 amino acids, representing amino acid residues 308-322, RIQRGPGRAFVTIGK, of env gp120 (HTLV-IIIB isolate). Five of the monoclonal antibodies raised to this antigen have reactivity with gp120 from divergent strains of HIV-1 in Western blot assays. The two of these five which were tested with live cells infected with the divergent HIV-1 isolates IIIB, MN, and RF were specifically reactive by fluorescence analyses with cells infected with the MN and IIIB isolates. Four of the five monoclonal antibodies blocked the fusion of IIIB-infected cells with uninfected MOLT-4 target cells. The monoclonal antibody most reactive with MN-infected cells by fluorescence, #5025A, blocked the fusion of MN-infected cells with uninfected MOLT-4 cells. Four of the five monoclonal antibodies neutralized the IIIB isolate of HIV-1 in vitro, but none neutralized the MN or RF isolates at the levels of antibody tested (less than or equal to 50 micrograms/ml). Taken together these data indicate that monoclonal antibodies to the immunodominant neutralizing domain of HIV-1 gp120 display different levels of group reactivity depending on the assay system being examined.

Authors
Durda, PJ; Bacheler, L; Clapham, P; Jenoski, AM; Leece, B; Matthews, TJ; McKnight, A; Pomerantz, R; Rayner, M; Weinhold, KJ
MLA Citation
Durda, PJ, Bacheler, L, Clapham, P, Jenoski, AM, Leece, B, Matthews, TJ, McKnight, A, Pomerantz, R, Rayner, M, and Weinhold, KJ. "HIV-1 neutralizing monoclonal antibodies induced by a synthetic peptide." AIDS Res Hum Retroviruses 6.9 (September 1990): 1115-1123.
PMID
1702301
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
6
Issue
9
Publish Date
1990
Start Page
1115
End Page
1123
DOI
10.1089/aid.1990.6.1115

Interpretation of western blots of specimens from children infected with human immunodeficiency virus type 1: implications for prognosis and diagnosis.

Authors
Walter, EB; McKinney, RE; Lane, BA; Weinhold, KJ; Wilfert, CM
MLA Citation
Walter, EB, McKinney, RE, Lane, BA, Weinhold, KJ, and Wilfert, CM. "Interpretation of western blots of specimens from children infected with human immunodeficiency virus type 1: implications for prognosis and diagnosis." J Pediatr 117.2 Pt 1 (August 1990): 255-258.
PMID
2380826
Source
pubmed
Published In
The Journal of Pediatrics
Volume
117
Issue
2 Pt 1
Publish Date
1990
Start Page
255
End Page
258

Human immunodeficiency virus-1 disease progression in hemophiliacs.

A retrospective study of 153 hemophiliacs infected with human immunodeficiency virus-1 (HIV-1) was performed to determine the clinical and immunological consequences of HIV-1 infection and the markers and cofactors associated with these changes. Nearly 80% of HIV-1-infected hemophiliacs have developed a significant reduction in their CD-4+ counts (less than 400 CD-4+ cells/mm3) with 40% having less than 200 CD-4+ cells/mm3 by the end of 1987. The rate of CD-4+ cell count decline was slightly greater in patients who have already developed the acquired immunodeficiency syndrome (AIDS) compared to those who have not (50 vs. 31 cells/mm3/6 months). Thrombocytopenia and older age were associated with a more rapid CD-4+ count deterioration, but the quantity of clotting factor utilized did not affect immunologic progression. In patients with less than 200 CD-4+ cells/mm3, the incidence of AIDS was significantly higher in adults (greater than 21 years old) compared to children/adolescents. Cytomegalovirus (CMV) seroprevalence increased with age but did not correlate with the amount of concentrated clotting factor used. Although there was no relationship between CMV status and progression to AIDS, CMV-seropositive patients were older and had a lower CD-4+ count. Thus the majority of HIV-1-infected hemophiliacs are developing progressive immune dysfunction measured by CD-4+ count decline. This drop in CD-4+ count significantly correlates with a risk for the development of AIDS in adults but not in children (less than 21 years old).

Authors
Becherer, PR; Smiley, ML; Matthews, TJ; Weinhold, KJ; McMillan, CW; White, GC
MLA Citation
Becherer, PR, Smiley, ML, Matthews, TJ, Weinhold, KJ, McMillan, CW, and White, GC. "Human immunodeficiency virus-1 disease progression in hemophiliacs." Am J Hematol 34.3 (July 1990): 204-209.
PMID
2163586
Source
pubmed
Published In
American Journal of Hematology
Volume
34
Issue
3
Publish Date
1990
Start Page
204
End Page
209

Alterations in antibody-dependent cellular cytotoxicity during the course of HIV-1 infection. Humoral and cellular defects.

HIV-1-specific cell-mediated cytotoxicity (CMC) is a form of antibody-dependent cellular cytotoxicity (ADCC) in which HIV-1-specific antibodies arm NK cells directly to become cytotoxic for targets bearing HIV-1 antigenic determinants. This non-MHC-restricted cytotoxic activity is present in early stages of disease and declines markedly with disease progression. To understand the cellular and humoral factors contributing to the reduction in this activity, the conditions under which maximal arming of cells occurs was examined in vitro. With the use of a large patient cohort, a strong positive correlation was found between the capacity of a serum to direct lysis in standard ADCC assays and its ability to arm NK cells. Patients with minimal HIV-1-specific ADCC-directing antibodies exhibited low levels of CMC and were unable to arm normal effector cells in vitro. The lack of sufficient ADCC-directing antibodies was found to be one cause of defective CMC in some patients. Unlike asymptomatics, only a weak positive correlation was found between arming and ADCC with sera from AIDS patients, indicating that a factor other than absolute HIV-1 specific antibody titer was responsible for decreased CMC in this patient population. Another group of patients was found to have diminished CMC despite the presence of antibodies in the serum that were fully capable of arming normal effector cells to become cytotoxic for gp120-expressing targets. When compared with those of normal individuals, lymphocytes from seropositive patients mediated significantly reduced levels of cytotoxicity in ADCC and arming assays with the use of a high titered HIV-1-specific serum. In both assay systems, the magnitude and frequency of dysfunction in antibody-dependent cytolysis was found to be greater among AIDS patients than among asymptomatic individuals. The demonstration of both cellular and humoral defects in the ability of seropositive individuals to manifest ADCC reactivities strongly suggests that HIV-1 infection may significantly compromise the effectiveness of this potentially important cytolytic reactivity in vivo.

Authors
Tyler, DS; Stanley, SD; Nastala, CA; Austin, AA; Bartlett, JA; Stine, KC; Lyerly, HK; Bolognesi, DP; Weinhold, KJ
MLA Citation
Tyler, DS, Stanley, SD, Nastala, CA, Austin, AA, Bartlett, JA, Stine, KC, Lyerly, HK, Bolognesi, DP, and Weinhold, KJ. "Alterations in antibody-dependent cellular cytotoxicity during the course of HIV-1 infection. Humoral and cellular defects." J Immunol 144.9 (May 1, 1990): 3375-3384.
PMID
2329275
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
144
Issue
9
Publish Date
1990
Start Page
3375
End Page
3384

Measurement of direct and indirect forms of anti-HIV-1 ADCC: implications for other retroviral disease.

Among the varied cytotoxic immune reactivities elicited as a result of HIV-1 infection are two forms of non-MHC restricted cytotoxicity--namely, indirect and direct ADCC. Since these reactivities are directed at both HIV-1 infected as well as gp120 coated targets, there is a potential for anti-HIV-1 ADCC to play both a beneficial as well as a pathogenic role in the natural history of HIV-1 disease. Resolution of these issues will be of great importance to the development of future preventive and interventive therapeutic strategies for AIDS. The direct and indirect forms of ADCC described herein are, most probably, not unique to HIV-1. In theory, any viral disease, retroviral or otherwise, in which high titers of anti-envelope antibodies persist in an environment rich in Fc-receptor bearing effector NK/K cells would be likely to have some component of direct ADCC as part of the host anti-viral response. With this in mind it is imperative that those researchers involved in characterizing cellular anti-viral cytotoxicities do not mistake direct ADCC for another form of CTL activity. These two highly potent reactivities operate independently and are subject to different control mechanisms, both positive and negative, anti-viral ADCC has too long been regarded as a strictly in vitro phenomenon with no in vivo counterpart. Our studies demonstrating direct forms of ADCC in infected patients will hopefully have some impact in forcing a careful re-evaluation of this extremely important issue.

Authors
Weinhold, KJ; Tyler, DS; Lyerly, HK
MLA Citation
Weinhold, KJ, Tyler, DS, and Lyerly, HK. "Measurement of direct and indirect forms of anti-HIV-1 ADCC: implications for other retroviral disease." Dev Biol Stand 72 (1990): 343-348.
PMID
2282991
Source
pubmed
Published In
Developments in Biologicals
Volume
72
Publish Date
1990
Start Page
343
End Page
348

Seroprevalence of human immunodeficiency virus infection at sentinel hospitals (II)

Authors
Shih, DP; Walter, EB; Drucker, RP; Greenwell, T; Wilfert, CM; Weinhold, KJ
MLA Citation
Shih, DP, Walter, EB, Drucker, RP, Greenwell, T, Wilfert, CM, and Weinhold, KJ. "Seroprevalence of human immunodeficiency virus infection at sentinel hospitals (II)." New England Journal of Medicine 323.26 (1990): 1843-1844.
PMID
2247127
Source
scival
Published In
New England Journal of Medicine
Volume
323
Issue
26
Publish Date
1990
Start Page
1843
End Page
1844

Safety and tolerance of intermittent intravenous and oral zidovudine therapy in human immunodeficiency virus-infected pediatric patients

Thirty-five children with symptomatic human immunodeficiency virus infection were enrollled in a 12-week, three-center phase I study of intravenous and oral zidovudine therapy. At enrollment the children ranged in age from 5 months to 13 years, with a median age of 3 1/2 years. Twenty-one children (60%) had acquired immunodeficiency syndrome and 14 (40%) had the related complex; 20 children had <0.5 10 9 CD4+ lymphocytes per liter (<500 cells/mm 3) at entry. Zidovudine was administered in one of three escalating dose regimens. One or two months of intravenous treatment with zidovudine every 6 hours was followed by orally administered drug on the same schedule; zidovudine was infused at 80, 120, or 160 mg/m 2/dose, and the oral dose was one and one-half times the intravenous dosage. Adverse events were similar to those observed in adults. Neutropenia (absolute neutrophil count <0.75 10 9/L (750 cells/mm 3) occurred in nine patients. The median neutrophil count fell from 2.50 10 9/L at entry to 1.72 10 9/L at the end of the study. Anemia requiring transfusion occurred in seven patients; the median hemoglobin level among nontransfused patients decreased from an entry value of 108 to 105 gm/L (10.8 to 10.5 gm/dl). Dosage adjustments were made in 15 patients, in 12 because of anemia or neutropenia. No patients required permanent discontinuation of zidovudine because of toxic effects. Positive effects included a faster-than-anticipated rate of weight gain, decreased hepatosplenomegaly, and lowering of the total IgG and IgM concentrations toward more normal values. Zidovudine appears to be safe and to have manageable toxic effects in children.

Authors
Jr, REM; Pizzo, PA; Scott, GB; Parks, WP; Maha, MA; Lehrman, SN; Riggs, M; Eddy, J; Lane, BA; Eppes, SC; al, E
MLA Citation
Jr, REM, Pizzo, PA, Scott, GB, Parks, WP, Maha, MA, Lehrman, SN, Riggs, M, Eddy, J, Lane, BA, Eppes, SC, and al, E. "Safety and tolerance of intermittent intravenous and oral zidovudine therapy in human immunodeficiency virus-infected pediatric patients." Journal of Pediatrics 116.4 (1990): 640-647.
Source
scival
Published In
Journal of Pediatrics
Volume
116
Issue
4
Publish Date
1990
Start Page
640
End Page
647

Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant

The principal neutralizing determinant (PND) of human immunodeficiency virus HIV-1 is part of a disulfide bridged loop in the third variable region of the external envelope protein, gp120. Analysis of the amino acid sequences of this domain from 245 different HIV-1 isolates revealed that the PND is less variable than thought originally. Conservation to better than 80 percent of the amino acids in 9 out of 14 positions in the central portion of the PND and the occurrence of particular oligopeptide sequences in a majority of the isolates suggest that there are constraints on PND variability. One constraining influence may be the structural motif (β strand - type II β turn - β strand - α helix) predicted for the consensus PND sequence by a neural network approach. Isolates with a PND similar to the commonly investigated human T cell lymphoma virus IIIB (HTLV-IIIB) and LAV-1 (BRU) strains were rare, and only 14 percent of sera from 86 randomly selected HIV-1 seropositive donors contained antibodies that recognized the PND of these virus isolates. In contrast, over 65 percent of these sera reacted with peptides containing more common PND sequences. These results suggest that HIV vaccine immunogens chosen because of their similarity to the consensus PND sequence and structure are likely to induce antibodies that neutralize a majority of HIV-1 isolates.

Authors
LaRosa, GJ; Davide, JP; Weinhold, K; Waterbury, JA; Profy, AT; Lewis, JA; Langlois, AJ; Dreesman, GR; Boswell, RN; Shadduck, P; Holley, LH; Karplus, M; Bolognesi, DP; Matthews, TJ; Emini, EA; Putney, SD
MLA Citation
LaRosa, GJ, Davide, JP, Weinhold, K, Waterbury, JA, Profy, AT, Lewis, JA, Langlois, AJ, Dreesman, GR, Boswell, RN, Shadduck, P, Holley, LH, Karplus, M, Bolognesi, DP, Matthews, TJ, Emini, EA, and Putney, SD. "Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant." Science 249.4971 (1990): 932-935.
PMID
2392685
Source
scival
Published In
Science
Volume
249
Issue
4971
Publish Date
1990
Start Page
932
End Page
935

Human monoclonal antibody that recognizes the V3 region of human immunodeficiency virus gp120 and neutralizes the human T-lymphotropic virus type IIIMN strain

We describe a human IgG1 monoclonal antibody (N701.9b) derived by Epstein-Barr virus transformation of B cells from a human immunodeficiency virus-seropositive asymptomatic donor. This antibody was shown to recognize the principal neutralizing domain contained within the V3 region of gp120 of the MN strain of human immunodeficiency virus and MN-like strains, as determined by binding to the PB-1 fragment of MN gp120 and to synthetic peptides corresponding to the V3 region of MN and related virus strains. The epitope identified by monoclonal antibody N701.9b was mapped to a segment of V3 containing at least 7 amino acids (amino acids 316-322), which is located in the "tip" and "right" side of the V3 loop of the MN strain. Furthermore, this antibody manifested potent type-specific fusion-inhibitory activity against the MN strain but not against the IIIB or RF virus strains. This antibody also neutralized four virus isolates that had MN-like V3 region sequences and failed to neutralize three other strains containing unrelated V3 region sequences. Our findings confirm that the V3 region stimulates type-specific neutralizing antibody during natural human immunodeficiency virus infection in humans. The potential clinical use of this antibody is discussed.

Authors
Jr, CFS; Silver, S; Profy, AT; Putney, SD; Langlois, A; Weinhold, K; Robinson, JE
MLA Citation
Jr, CFS, Silver, S, Profy, AT, Putney, SD, Langlois, A, Weinhold, K, and Robinson, JE. "Human monoclonal antibody that recognizes the V3 region of human immunodeficiency virus gp120 and neutralizes the human T-lymphotropic virus type IIIMN strain." Proceedings of the National Academy of Sciences of the United States of America 87.21 (1990): 8597-8601.
PMID
1700435
Source
scival
Published In
Proceedings of the National Academy of Sciences of USA
Volume
87
Issue
21
Publish Date
1990
Start Page
8597
End Page
8601

Anti-HIV-1 ADCC.

Authors
Tyler, DS; Lyerly, HK; Weinhold, KJ
MLA Citation
Tyler, DS, Lyerly, HK, and Weinhold, KJ. "Anti-HIV-1 ADCC." AIDS Res Hum Retroviruses 5.6 (December 1989): 557-563. (Review)
PMID
2692657
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
5
Issue
6
Publish Date
1989
Start Page
557
End Page
563
DOI
10.1089/aid.1989.5.557

Cytokine augmentation of human immunodeficiency virus type 1 (HIV-1) gp120-specific cellular cytotoxicity.

Currently available anti-human immunodeficiency virus type 1 (HIV-1) agents such as azidothymidine can prevent de novo virus infection in vitro but lack significant activity against chronically infected cells. Our laboratory has recently described glycoprotein (gp)120-specific cell mediated cytotoxicity (CMC) present in HIV-1-seropositive individuals that is capable of destroying virally infected cells. As a means of potentially eliminating persistent reservoirs of HIV-1, we examined the ability of various cytokines to augment preexisting gp120-specific CMC activity of peripheral blood mononuclear cells obtained from early disease patients. We found that interferon-gamma alone had no effect on gp120 cellular reactivity; however, the combination of interferon-gamma plus IL-2 produced enhancement beyond that of IL-2 alone.

Authors
Stine, KC; Bolognesi, D; Weinhold, KJ
MLA Citation
Stine, KC, Bolognesi, D, and Weinhold, KJ. "Cytokine augmentation of human immunodeficiency virus type 1 (HIV-1) gp120-specific cellular cytotoxicity." J Biol Response Mod 8.5 (October 1989): 501-510.
PMID
2552026
Source
pubmed
Published In
Journal of Biological Response Modifiers
Volume
8
Issue
5
Publish Date
1989
Start Page
501
End Page
510

EXVIVO ACTIVATION OF CELLULAR CYTO-TOXIC RESPONSES IN HIV-1 INFECTED PATIENTS

Authors
STINE, KC; TYLER, DS; STANLEY, SD; BOLOGNESI, DP; WEINHOLD, KJ
MLA Citation
STINE, KC, TYLER, DS, STANLEY, SD, BOLOGNESI, DP, and WEINHOLD, KJ. "EXVIVO ACTIVATION OF CELLULAR CYTO-TOXIC RESPONSES IN HIV-1 INFECTED PATIENTS." June 1989.
Source
wos-lite
Published In
Journal of Biological Response Modifiers
Volume
8
Issue
3
Publish Date
1989
Start Page
333
End Page
333

HIV-1 GP120-mediated immune suppression and lymphocyte destruction in the absence of viral infection.

The magnitude of immunologic defects observed in HIV-1-infected individuals before the development of overt AIDS is disproportionately high in comparison to the levels of infectious virus in these patients--suggesting that factors other than direct virus-induced cytopathology may be involved. With this in mind, we investigated the immunologic consequences of the interaction between purified HIV-1 gp120 and the CD4 molecules expressed by uncommitted as well as Ag-specific lymphocytes. HIV-1 gp120 exhibited a dose-dependent immunosuppressive effect on: 1) Ag-driven proliferation of cloned CD4+ lymphocytes, 2) OKT3-driven proliferation of cloned CD4+ lymphocytes, and 3) cytolytic activity of CD4+, EBV-specific CTL. Thus, HIV-1 gp120 can, in a manner similar to OKT4A antibodies, suppress T cell activation and the expression of cytolytic activities through its interaction with CD4. Additionally, activated CD4+ lymphoblasts can be rendered susceptible to immune cytolysis by virtue of their binding of purified gp120. This "targeting" of activated lymphoblasts can occur with levels of gp120 far below that which is needed to saturate all OKT4A-defined CD4 epitopes. Adsorbed gp120 could be demonstrated on the surface of these cells for up to 12 h, a sufficient time for interaction with host cytolytic elements. The data from these in vitro modeling experiments highlight one of many potential mechanisms of HIV-1 induced immunosuppression and lymphocyte destruction that can occur in the absence of infectious virus and that is based on the unique interaction between HIV-1 gp120 and its cellular receptor, CD4.

Authors
Weinhold, KJ; Lyerly, HK; Stanley, SD; Austin, AA; Matthews, TJ; Bolognesi, DP
MLA Citation
Weinhold, KJ, Lyerly, HK, Stanley, SD, Austin, AA, Matthews, TJ, and Bolognesi, DP. "HIV-1 GP120-mediated immune suppression and lymphocyte destruction in the absence of viral infection." J Immunol 142.9 (May 1, 1989): 3091-3097.
PMID
2468713
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
142
Issue
9
Publish Date
1989
Start Page
3091
End Page
3097

GP120 specific cellular cytotoxicity in HIV-1 seropositive individuals. Evidence for circulating CD16+ effector cells armed in vivo with cytophilic antibody.

Fresh circulating PBMC from HIV-1 seropositive individuals have been found to mediate specific, non-MHC restricted lysis of targets expressing the major envelope glycoprotein of HIV-1, gp120, in 6-h 51Cr release assays. This gp120 specific cell-mediated cytotoxicity (CMC) is broadly reactive against target cells infected with a wide range of viral isolates, is IL-2 augmentable, and is mediated by a CD16+, Leu-7+, CD15-, CD3- population of NK/K cells. The presence of FcR (CD16) on these cells suggested that the lytic specificity for gp120 might be directed by cytophilic antibody bound to the cell surface. Affinity purified F(ab')2 antibody fragments specific for the Fc and F(ab')2 portions of human IgG were used in attempts to block gp120 specific lysis. A 1/50 dilution of these antibodies inhibited gp120 specific cytolytic activity by more than 90% while exhibiting a minimal effect on NK/K cell lysis of K562 targets. The blocking activity of these fragments demonstrates the direct involvement of cytophilic antibody in CMC. In attempts to isolate this cytophilic anti-HIV-1 antibody, short 56 degrees C incubations were used to dissociate antibodies from the surface of PBMC of seropositive individuals. The supernatants generated in this manner exhibited specific gp120 activity in antibody-dependent cellular cytotoxicity assays. The ability of Staphylococcal protein A to remove this activity confirms the presence of cytophilic antibody on freshly isolated PBMC. Selective enrichment of specific cell subpopulations revealed the origin of the cytophilic antibody to be CD16+ NK/K cells and not B cells, T cells, or monocytes/macrophages. These studies show that the gp120-specific CMC seen in HIV-1 seropositive individuals is directed by cytophilic antibody bound to circulating CD16+ NK/K cells and represents a form of direct antibody-dependent cellular cytotoxicity which may provide a primary cytotoxic host defense.

Authors
Tyler, DS; Nastala, CL; Stanley, SD; Matthews, TJ; Lyerly, HK; Bolognesi, DP; Weinhold, KJ
MLA Citation
Tyler, DS, Nastala, CL, Stanley, SD, Matthews, TJ, Lyerly, HK, Bolognesi, DP, and Weinhold, KJ. "GP120 specific cellular cytotoxicity in HIV-1 seropositive individuals. Evidence for circulating CD16+ effector cells armed in vivo with cytophilic antibody." J Immunol 142.4 (February 15, 1989): 1177-1182.
PMID
2536767
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
142
Issue
4
Publish Date
1989
Start Page
1177
End Page
1182

The antiretroviral effects of lymphokine-activated killer cells

Authors
Tyler, DS; Stanley, SD; Bumpas, EA; Bartlett, JA; Bolognesi, DP; Weinhold, KJ
MLA Citation
Tyler, DS, Stanley, SD, Bumpas, EA, Bartlett, JA, Bolognesi, DP, and Weinhold, KJ. "The antiretroviral effects of lymphokine-activated killer cells." 1989.
Source
scival
Published In
Surgical Forum
Volume
40
Publish Date
1989
Start Page
435
End Page
437

The role of bone marrow and thymic elements in the initiation and spread of virus production in the AKR thymus.

Passive anti-viral immunotherapy greatly suppresses the incidence of spontaneous leukemia in AKR mice, rendering the thymus of successfully treated animals devoid of infectious ecotropic retrovirus. Reconstitution assays have determined that the thymic and splenic homing cells of the AKR bone marrow become ecotropic virus producers subsequent to their seeding of these hematopoietic organs and that in vitro depletion of gp71 expressing bone marrow cells reduces stem cell numbers without affecting prothymocyte content. In the thymus, a population of radioresistant cells, which phenotypically resemble cortical thymocytes, but are unique in their expression of high levels of H-2Kk antigen, have been found to produce high levels of both ecotropic and MCF virus and have been implicated as a putative therapeutic target cell population of anti-viral treatment. In addition, the failure of treated animals to reconstitute following lethal irradiation suggests that an immunotherapy-induced alteration occurs in the bone marrow of AKR mice.

Authors
Buckheit, RW; Bolognesi, DP; Weinhold, KJ
MLA Citation
Buckheit, RW, Bolognesi, DP, and Weinhold, KJ. "The role of bone marrow and thymic elements in the initiation and spread of virus production in the AKR thymus." Virology 166.2 (October 1988): 533-541.
PMID
3176345
Source
pubmed
Published In
Virology
Volume
166
Issue
2
Publish Date
1988
Start Page
533
End Page
541

Phenotypic variation in the response to the human immunodeficiency virus among derivatives of the CEM T and WIL-2 B cell lines.

Derivatives of the CEM T and WIL-2 B cell lines showed striking diversity in their responses to the HTLV-IIIB strain of the human immunodeficiency virus (HIV). Several stable phenotypic patterns could be defined, based on whether cells were permissive (P+, P-) for virus production, were sensitive or insensitive to cytopathic effects after infection by free virus (C+, C-), and whether they underwent fusion on contact with virus-infected cells (F+, F-). Although expression of CD4 was essential for infection by HTLV-IIIB, very low levels were sufficient for productive infection of WIL-2 derivatives. Conversely, some CEM T cell lines that expressed ample CD4, and which were able to bind virus gp120 and undergo fusion, did not support productive infection by free virus. One nonpermissive, CD4+ derivative of CEM could bind gp120 but failed to undergo fusion, suggesting an alteration in some membrane protein other than CD4 that is essential for virus entry and HIV-induced cell fusion. The AA2 derivative of the WIL-2 cell line is also described, which is remarkably permissive for HIV replication and exquisitely sensitive to virus cytopathic effect. The panel of related cell lines with different host-virus phenotypes could be useful for more precisely defining steps in the infectious cycle of HIV, and for identifying host cell genes and gene products that determine the outcome of HIV infection.

Authors
Chaffee, S; Leeds, JM; Matthews, TJ; Weinhold, KJ; Skinner, M; Bolognesi, DP; Hershfield, MS
MLA Citation
Chaffee, S, Leeds, JM, Matthews, TJ, Weinhold, KJ, Skinner, M, Bolognesi, DP, and Hershfield, MS. "Phenotypic variation in the response to the human immunodeficiency virus among derivatives of the CEM T and WIL-2 B cell lines." J Exp Med 168.2 (August 1, 1988): 605-621.
PMID
3261775
Source
pubmed
Published In
The Journal of Experimental Medicine
Volume
168
Issue
2
Publish Date
1988
Start Page
605
End Page
621

Cellular immune response to viral peptides in patients exposed to HIV.

In efforts to identify B cell and T cell epitopes of HIV-1 structural components, serum as well as lymphocytes from HIV-1-seropositive individuals were reacted with several recombinant and native peptides representing defined viral gag and env determinants. Several areas of discordance between humoral and cellular reactivity were identified. Specifically, the principal neutralizing site within HIV-1, the major envelope glycoprotein gp120, failed to elicit detectable cellular reactivities. The carboxyl portion of gp120 and the transmembrane gp41 region were uniformly recognized by patient antibodies but did not produce significant lymphocyte blastogenesis. However, the amino half of gp120 elicited cellular responses in a majority of the immunocompetent individuals tested, despite its extremely low reactivity with patient sera. Last, the major HIV-1 structure component p24 was found to be the most consistent T cell activation antigen among the panel tested.

Authors
Ahearne, PM; Matthews, TJ; Lyerly, HK; White, GC; Bolognesi, DP; Weinhold, KJ
MLA Citation
Ahearne, PM, Matthews, TJ, Lyerly, HK, White, GC, Bolognesi, DP, and Weinhold, KJ. "Cellular immune response to viral peptides in patients exposed to HIV." AIDS Res Hum Retroviruses 4.4 (August 1988): 259-267.
PMID
2462895
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
4
Issue
4
Publish Date
1988
Start Page
259
End Page
267
DOI
10.1089/aid.1988.4.259

Characteristics of a neutralizing monoclonal antibody to the HIV envelope glycoprotein.

We have studied the biologic and physical properties of a monoclonal antibody that binds to gp120, the exterior envelope glycoprotein of the human immunodeficiency virus (HIV) strain HTLV-IIIB. Designated 9284, the antibody possesses viral neutralizing activity and inhibits syncytium formation by infected cells. The antibody recognized a region of the polypeptide backbone previously described as an important neutralizing epitope. This region lies 307-330 residues from amino terminus of the glycoprotein. We have compared the biologic and physical properties of this antibody to those of the recently described 0.5 beta monoclonal antibody to gp120. The 0.5 beta antibody was biologically more potent and bound an epitope slightly downstream to that of the 9284 antibody. The antibodies did not differ significantly in their affinity for gp120. In competition studies, the 0.5 beta antibody was displaced by the 9284 antibody, but the binding of the latter was unaffected by 0.5 beta.

Authors
Skinner, MA; Ting, R; Langlois, AJ; Weinhold, KJ; Lyerly, HK; Javaherian, K; Matthews, TJ
MLA Citation
Skinner, MA, Ting, R, Langlois, AJ, Weinhold, KJ, Lyerly, HK, Javaherian, K, and Matthews, TJ. "Characteristics of a neutralizing monoclonal antibody to the HIV envelope glycoprotein." AIDS Res Hum Retroviruses 4.3 (June 1988): 187-197.
PMID
2456088
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
4
Issue
3
Publish Date
1988
Start Page
187
End Page
197
DOI
10.1089/aid.1988.4.187

Transmission of human immunodeficiency virus to sexual partners of hemophiliacs.

To examine the variables associated with heterosexual transmission of human immunodeficiency virus (HIV), we studied 32 couples in our hemophilia center who had steady sexual relationships for periods more than 1 year. Of the 32 sexual partners of the hemophiliacs, five (15.6%) were HIV seropositive. All five hemophiliacs with HIV transmission to their sexual partners had measurable immunologic deficiencies, as shown by their lower median T-helper (CD-4+) lymphocyte count of 172 cells/mm3. The hemophiliacs without transmission had a slightly higher median CD-4+ count of 297 cells/mm3 (P = .26). To determine if factors other than the degree of immunologic deficiency in the hemophiliac might contribute to HIV transmission, 18 of the 32 couples were studied more intensively by confidential, coded questionnaires. Regular condom use was reported by nine couples (50%). Two of nine women (22%) without condom usage acquired HIV. One of nine women (11%) using condoms was seropositive; she also reported eight needlestick injuries while assisting her spouse with clotting factor treatments. Intravenous drug abuse was reported in two of the five couples with HIV transmission. Thus, hemophiliacs are at risk for transmitting HIV parenterally as well as venereally. Despite various risk behaviours associated with HIV transmission, the prevalence of infection in our cohort of hemophiliacs' sexual partners is low and within the range (6.8-22%) reported by others. This study underscores the need for comprehensive education and counseling in what previously appeared to be a homogeneous clinic population at risk for transmitting HIV to others.

Authors
Smiley, ML; White, GC; Becherer, P; Macik, G; Matthews, TJ; Weinhold, KJ; McMillan, C; Bolognesi, D
MLA Citation
Smiley, ML, White, GC, Becherer, P, Macik, G, Matthews, TJ, Weinhold, KJ, McMillan, C, and Bolognesi, D. "Transmission of human immunodeficiency virus to sexual partners of hemophiliacs." Am J Hematol 28.1 (May 1988): 27-32.
PMID
3369433
Source
pubmed
Published In
American Journal of Hematology
Volume
28
Issue
1
Publish Date
1988
Start Page
27
End Page
32

Cellular anti-GP120 cytolytic reactivities in HIV-1 seropositive individuals.

Forty-one patients seropositive for human immunodeficiency virus type 1 (HIV-1) were assessed for cell-mediated cytotoxicity (CMC) against autologous target cells bearing the major envelope glycoprotein of HIV-1, gp120. Effector lymphocytes from over 85% of seropositive patients showed CMC specific for gp120-coated targets, whereas seronegative individuals had no detectable CMC. As a group, symptomless individuals had the highest levels of CMC; patients with AIDS-related complex and AIDS showed progressively diminished reactivity. The gp120-specific CMC was mediated by a population of non-T-cell effectors phenotypically resembling NK/K cells. Cytolysis was not restricted by major histocompatibility complex determinants, as shown by killing of heterologous gp120-adsorbed targets and of HIV-1-infected cell-lines. Gp120-specific CMC was highly augmented in the presence of interleukin 2, so it may be possible to develop therapeutic strategies aimed at destruction of virus-producing cell reservoirs in infected individuals through stimulation of HIV-specific host CMC.

Authors
Weinhold, KJ; Lyerly, HK; Matthews, TJ; Tyler, DS; Ahearne, PM; Stine, KC; Langlois, AJ; Durack, DT; Bolognesi, DP
MLA Citation
Weinhold, KJ, Lyerly, HK, Matthews, TJ, Tyler, DS, Ahearne, PM, Stine, KC, Langlois, AJ, Durack, DT, and Bolognesi, DP. "Cellular anti-GP120 cytolytic reactivities in HIV-1 seropositive individuals." Lancet 1.8591 (April 23, 1988): 902-905.
PMID
2895830
Source
pubmed
Published In
The Lancet
Volume
1
Issue
8591
Publish Date
1988
Start Page
902
End Page
905

Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides.

A synthetic peptide (SP-10-IIIB) with an amino acid sequence [Cys-Thr-Arg-Pro-Asn-Asn-Asn-Thr-Arg-Lys-Ser-Ile-Arg-Ile-Gln-Arg-Gly-Pro -Pro-Gly-(Tyr); amino acids 303-321] from the human immunodeficiency virus (HIV) isolate human T-cell lymphotropic virus type III (HTLV-III) HTLV-IIIB envelope glycoprotein gp120 was coupled to tetanus toxoid and used to raise goat antibodies to HIV gp120. Goat anti-SP-10-IIIB serum bound to the surface of HTLV-IIIB-infected CEM T cells but not to the surface of HTLV-IIIRF-infected or uninfected CEM T cells. Anti-SP-10-IIIB antibodies also selectively bound to gp120 from lysates of HTLV-IIIB cells in immunoblot assays. Twenty-one percent of sera (28 of 175) from patients seropositive for HIV contained antibodies that reacted with SP-10-IIIB in RIA. Human anti-SP-10-IIIB antibodies affinity purified from acquired immunodeficiency syndrome (AIDS) patient serum bound to HTLV-IIIB-infected cells and immunoprecipitated gp120. Goat antibodies to SP-10-IIIB neutralized HTLV-IIIB (80% neutralization titer of 1/600), inhibited HTLV-IIIB-induced syncytium formation, but did not neutralize HIV isolates HTLV-IIIRF or HTLV-IIIMN or inhibit syncytium formation with these isolates. Also, goat antiserum to an homologous synthetic peptide [SP-10-IIIRF(A), (Cys)-Arg-Lys-Ser-Ile-Thr-Lys-Gly-Pro-Gly-Arg-Val-Ile-Tyr] from gp120 of HIV isolate HTLV-IIIRF inhibited syncytium formation by HTLV-IIIRF, but did not inhibit syncytium formation by HTLV-IIIB or by HTLV-IIIMN. Thus, the amino acid sequences of SP-10-IIIB and SP-10-IIIRF(A) define homologous regions of gp120 that are important in type-specific virus neutralization. The identification of these type-specific neutralizing epitopes should facilitate the design of a polyvalent, synthetic vaccine for AIDS.

Authors
Palker, TJ; Clark, ME; Langlois, AJ; Matthews, TJ; Weinhold, KJ; Randall, RR; Bolognesi, DP; Haynes, BF
MLA Citation
Palker, TJ, Clark, ME, Langlois, AJ, Matthews, TJ, Weinhold, KJ, Randall, RR, Bolognesi, DP, and Haynes, BF. "Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides." Proc Natl Acad Sci U S A 85.6 (March 1988): 1932-1936.
PMID
2450351
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
85
Issue
6
Publish Date
1988
Start Page
1932
End Page
1936

Detection of HIV-1 neutralizing antibodies by a simple, rapid, colorimetric assay.

A rapid, simple, reproducible and semi-quantitative assay to measure neutralizing antibodies has been developed. It employs a unique cell line which is exquisitively sensitive to infection with all HIV isolates tested. The assay is amenable to microtiter formulation as well as analysis by automation.

Authors
Langlois, AJ; Matthews, TJ; Weinhold, KJ; Chaffee, S; Hershfield, M; Bolognesi, DP
MLA Citation
Langlois, AJ, Matthews, TJ, Weinhold, KJ, Chaffee, S, Hershfield, M, and Bolognesi, DP. "Detection of HIV-1 neutralizing antibodies by a simple, rapid, colorimetric assay." AIDS Res Hum Retroviruses 4.1 (February 1988): 63-69.
PMID
3163254
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
4
Issue
1
Publish Date
1988
Start Page
63
End Page
69
DOI
10.1089/aid.1988.4.63

The coenrichment of stem cells, prothymocytes, and stromal elements with ecotropic retrovirus-producing cells from the bone marrow of leukemia-prone AKR mice.

Ecotropic virus-producing cells in the bone marrow of the leukemia-prone AKR strain of mice were significantly enriched by fractionation on discontinuous density gradients of Percoll and were found in a low-density population of cells comprised predominantly of medium to large blast cells. The high ecotropic virus-producing low-density bone marrow cell population was also found to be significantly enriched in pluripotent stem cells, prothymocytes, and stromal elements. During the period of time defined by a window for successful leukemosuppressive immunotherapy of AKR mice, virus-producing cells were exclusively detected in this fraction of bone marrow cells, implicating the functional classes of cells coenriched in this fraction as both potential targets of anti-viral immunotherapy and responsible for the seeding of the spleen and thymus with infectious ecotropic virus.

Authors
Buckheit, RW; Kurtzberg, J; Bolognesi, DP; Weinhold, KJ
MLA Citation
Buckheit, RW, Kurtzberg, J, Bolognesi, DP, and Weinhold, KJ. "The coenrichment of stem cells, prothymocytes, and stromal elements with ecotropic retrovirus-producing cells from the bone marrow of leukemia-prone AKR mice." Virology 162.2 (February 1988): 354-361.
PMID
2829423
Source
pubmed
Published In
Virology
Volume
162
Issue
2
Publish Date
1988
Start Page
354
End Page
361

Loss of tumorigenicity following in vitro MuLV infection is associated with induction of peritoneal natural killer cell activity.

Infection by an attenuated replication-competent murine retrovirus (Friend leukemia virus-FLV4), but not other non-transforming retroviruses, stimulated rejection of transplantable thymomas (RL-cell line) and subsequent tumor immunity in syngeneic mouse recipients. FLV-infected RL-cells (RL-FLV) were unaltered in their in vitro growth, and grew progressively to kill sublethally irradiated animals and nude mice. Primary RL-FLV rejection was due to induction of increased natural killer (NK)-cell activity limited to peritoneal sites of tumor inoculation with a minor cytolytic macrophage population. Syngeneic mutant beige (NK-deficient) mice similarly rejected RL-FLV cells with increased peritoneal NK-cell activity and acquired immunity to the parental RL-tumor. While RL-FLV stimulated far greater peritoneal NK activity than did other tested retrovirus-infected RL-cells, the inherent susceptibility of these cells to lysis by normal NK cells was not altered by virus. RL-FLV induced NK effectors showed an indiscriminate lysis pattern that was independent of target cell type and retrovirus expression.

Authors
Thiel, K; Genovesi, EV; Iglehart, JD; Bolognesi, DP; Weinhold, KJ
MLA Citation
Thiel, K, Genovesi, EV, Iglehart, JD, Bolognesi, DP, and Weinhold, KJ. "Loss of tumorigenicity following in vitro MuLV infection is associated with induction of peritoneal natural killer cell activity." Adv Exp Med Biol 239 (1988): 169-183.
PMID
2849290
Source
pubmed
Published In
Advances in experimental medicine and biology
Volume
239
Publish Date
1988
Start Page
169
End Page
183

The effects of leukemosuppressive immunotherapy on thymic infectious cell centers in AKR mice.

Although cortical thymocytes were found to be the predominant ecotropic and MCF-virus producers in the thymus of leukemia prone AKR mice the initial ecotropic retrovirus producing cells have been detected among a low density subpopulation of thymocytes including both PNA(+) and PNA(-) cells. Leukemosuppressive anti-viral treatment of these animals results in several important changes in the AKR thymus, including the elimination of virus producing cells, the induction of cellular phenotypic alterations, a decreased ability to bind ecotropic and MCF virus, a resistance to challenge with leukemogenic exogenous retroviruses, and the apparent elimination of a population of virus producing radioresistant cells. In addition, complement-mediated depletion with anti-viral IgG resulted in the complete elimination of proliferating thymocytes. These results suggest that passive anti-viral immunotherapy effectively eliminates a population of thymocytes which serve as the neonatal source of endogenous retroviruses and interferes with the earliest stages of leukemogenesis in AKR mice.

Authors
Buckheit, RW; Liberman, SN; Bolognesi, DP; Weinhold, KJ
MLA Citation
Buckheit, RW, Liberman, SN, Bolognesi, DP, and Weinhold, KJ. "The effects of leukemosuppressive immunotherapy on thymic infectious cell centers in AKR mice." Thymus 12.3 (1988): 143-156.
PMID
3266951
Source
pubmed
Published In
Thymus
Volume
12
Issue
3
Publish Date
1988
Start Page
143
End Page
156

Anti-HIV-1 immune cytolysis is independent of viral envelope glycosylation

Authors
Lyerly, HK; Skinner, MA; Tyler, DS; Nastala, CL; Matthews, TJ; Bolognesi, DP; Weinhold, KJ
MLA Citation
Lyerly, HK, Skinner, MA, Tyler, DS, Nastala, CL, Matthews, TJ, Bolognesi, DP, and Weinhold, KJ. "Anti-HIV-1 immune cytolysis is independent of viral envelope glycosylation." Surgical Forum 39 (1988): 420-422.
Source
scival
Published In
Surgical Forum
Volume
39
Publish Date
1988
Start Page
420
End Page
422

Direct antibody-dependent cellular cytotoxicity: Evidence of circulating antibody-armed cytotoxic CD16+ NK/K cells in patients infected with HIV-1

Authors
Tyler, DS; Nastala, CL; Lyerly, HK; Matthews, TJ; Bolognesi, DP; Weinhold, KJ
MLA Citation
Tyler, DS, Nastala, CL, Lyerly, HK, Matthews, TJ, Bolognesi, DP, and Weinhold, KJ. "Direct antibody-dependent cellular cytotoxicity: Evidence of circulating antibody-armed cytotoxic CD16+ NK/K cells in patients infected with HIV-1." Surgical Forum 39 (1988): 418-420.
Source
scival
Published In
Surgical Forum
Volume
39
Publish Date
1988
Start Page
418
End Page
420

3'-Azido-3'-deoxythymidine triphosphate as an inhibitor and substrate of purified human immunodeficiency virus reverse transcriptase.

Reverse transcriptase was purified from human immunodeficiency virus (HIV). It utilized the artificial primer-template poly(rA)-oligo(dT)12-18 more efficiently than activated calf thymus DNA, poly(rI)-oligo(dC)12-18, poly(rC)-oligo(dG)12-18, or poly(rCm)-oligo(dG)12-18. Maximum activity was observed at pH 7.0 to 7.6 in the presence of 5 mM MgCl2 and 100 mM KCl. 3'-Azido-3'-deoxythymidine triphosphate competed with dTTP for binding to HIV reverse transcriptase. Different kinetic constants were obtained with different primer-templates. Km and Ki values of 2.8 and 0.04 microM, respectively, were obtained with poly(rA)-oligo(dT)12-18. The corresponding values were 1.2 and 0.3 microM, respectively, with activated calf thymus DNA and 0.3 and 0.01 microM, respectively, with extracted virus and native template. Inhibition of the host cell DNA polymerases alpha and beta was considerably weaker. The Km and Ki values obtained with activated calf thymus DNA as the primer-template were 2.4 and 230 microM, respectively, for DNA polymerase alpha and 6.0 and 73 microM, respectively, for DNA polymerase beta. 3'-Azido-3'-deoxythymidine triphosphate could also serve as an alternate substrate for HIV reverse transcriptase. The resulting incorporation of 3'-azido-3'-deoxythymidine triphosphate into poly(rA)-oligo(dT)12-18 caused chain termination and premature deceleration of the reaction. The terminated primer could not be elongated when incubated with dTTP and HIV reverse transcriptase.

Authors
St Clair, MH; Richards, CA; Spector, T; Weinhold, KJ; Miller, WH; Langlois, AJ; Furman, PA
MLA Citation
St Clair, MH, Richards, CA, Spector, T, Weinhold, KJ, Miller, WH, Langlois, AJ, and Furman, PA. "3'-Azido-3'-deoxythymidine triphosphate as an inhibitor and substrate of purified human immunodeficiency virus reverse transcriptase." Antimicrob Agents Chemother 31.12 (December 1987): 1972-1977.
PMID
2449866
Source
pubmed
Published In
Antimicrobial agents and chemotherapy
Volume
31
Issue
12
Publish Date
1987
Start Page
1972
End Page
1977

Interaction between the human T-cell lymphotropic virus type IIIB envelope glycoprotein gp120 and the surface antigen CD4: role of carbohydrate in binding and cell fusion.

Interactions between retroviruses associated with acquired immunodeficiency syndrome and their receptors on lymphocytes represent the initial steps in the process of infection and are also involved in multinucleated giant cell formation, which is one form of virus-mediated cytopathology. The exterior envelope glycoprotein of the retrovirus has been identified as gp120, and we demonstrate here that purified gp120 binds directly to cells expressing the CD4 (T4) surface antigen at a site spatially related to that recognized by the OKT4A monoclonal antibody. The gp120 was also able to temporarily interfere with viral infection and to block the process of multinucleated giant cell formation. However, if the carbohydrate chains were removed from gp120 by enzymatic treatment, CD4 binding and blockade of cell fusion was reduced by about a factor of 50. The significance of these results in relation to preventive and interventive approaches for acquired immunodeficiency syndrome is discussed.

Authors
Matthews, TJ; Weinhold, KJ; Lyerly, HK; Langlois, AJ; Wigzell, H; Bolognesi, DP
MLA Citation
Matthews, TJ, Weinhold, KJ, Lyerly, HK, Langlois, AJ, Wigzell, H, and Bolognesi, DP. "Interaction between the human T-cell lymphotropic virus type IIIB envelope glycoprotein gp120 and the surface antigen CD4: role of carbohydrate in binding and cell fusion." Proc Natl Acad Sci U S A 84.15 (August 1987): 5424-5428.
PMID
3037551
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
84
Issue
15
Publish Date
1987
Start Page
5424
End Page
5428

Human T-cell lymphotropic virus IIIB glycoprotein (gp120) bound to CD4 determinants on normal lymphocytes and expressed by infected cells serves as target for immune attack.

The lymphocyte differentiation antigen CD4 serves as a receptor for human retroviruses associated with acquired immunodeficiency syndrome (AIDS) through its interaction with the major envelope virion glycoprotein, gp120, which is also expressed on the surface of infected cells. In these experiments, purified gp120 was shown to bind to normal human T-lymphocyte populations. The gp120-CD4 complex served as a target antigen for antibody-dependent complement-mediated cytolysis by a goat serum raised against native gp120. However, patient sera that bound to gp120-adsorbed cells failed to direct their destruction in the presence of complement. In contrast, these sera were potent mediators of antibody-dependent cellular cytotoxicity. These studies demonstrate that gp120 situated on the cell surface can serve as an effective target for immune destruction by patient antibodies and effector lymphocytes. The possible contribution of this type of immunity to control of disease progression, on the one hand, and to lymphocyte destruction and immunopathology observed in AIDS, on the other, is discussed.

Authors
Lyerly, HK; Matthews, TJ; Langlois, AJ; Bolognesi, DP; Weinhold, KJ
MLA Citation
Lyerly, HK, Matthews, TJ, Langlois, AJ, Bolognesi, DP, and Weinhold, KJ. "Human T-cell lymphotropic virus IIIB glycoprotein (gp120) bound to CD4 determinants on normal lymphocytes and expressed by infected cells serves as target for immune attack." Proc Natl Acad Sci U S A 84.13 (July 1987): 4601-4605.
PMID
3037522
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
84
Issue
13
Publish Date
1987
Start Page
4601
End Page
4605

The effects of leukemosuppressive immunotherapy on bone marrow infectious cell centers in AKR mice.

The bone marrow of AKR mice is the richest source of infectious ecotropic cell centers (ICCs) during the neonatal period. The bone marrow ICCs reside in a low-density population expressing high levels of viral glycoprotein (gp71) and Class I histocompatibility antigens (H-2Kk). In addition, ICCs are enriched in the lymphoid band of Ficoll-Hypaque-fractionated bone marrow, the adherent population of nylon wool separated cells and among the low-density subpopulation of Percoll-fractionated marrow. The observed dichotomy between viral antigen expression and actual virus production suggests that actively cycling cells may be the primary virus producers in the AKR bone marrow. The phenotypic and physical data indicate that bone marrow stem cells and/or prothymocytes may be among the initial virus producing cells in the AKR bone marrow. Leukemosuppressive antiviral immunotherapy delays the appearance of ICCs in the bone marrow but does not exert any major long-term changes on the populations of cells present.

Authors
Buckheit, RW; Bolognesi, DP; Weinhold, KJ
MLA Citation
Buckheit, RW, Bolognesi, DP, and Weinhold, KJ. "The effects of leukemosuppressive immunotherapy on bone marrow infectious cell centers in AKR mice." Virology 157.2 (April 1987): 387-396.
PMID
3029979
Source
pubmed
Published In
Virology
Volume
157
Issue
2
Publish Date
1987
Start Page
387
End Page
396

Management of human immunodeficiency virus-associated thrombocytopenia with intravenous gamma globulin.

A 17-month-old boy in whom immune-mediated thrombocytopenia (ITP) was the presenting manifestation of infection with human immunodeficiency virus (HIV) is being successfully managed with intermittent high-dose intravenous gamma globulin (IVIG) allowing maintenance of hemostatic platelet counts while avoiding the immunosuppression associated with other therapeutic modalities used to treat ITP. He continues to demonstrate marked responsiveness to IVIG, and has been maintained on weekly or bimonthly infusions for 12 months. The serendipitous documentation of HIV infection prior to IVIG therapy for immune-mediated thrombocytopenia in this child documents the importance of HIV testing prior to IVIG therapy to prevent erroneous assignment of IVIG as the vehicle responsible for transmission of HIV infection. This case history also documents the importance of HIV testing in the diagnostic evaluation of immune-mediated thrombocytopenias.

Authors
Kurtzberg, J; Friedman, HS; Kinney, TR; Chaffee, S; Stine, K; Falletta, JM; Weinhold, KJ
MLA Citation
Kurtzberg, J, Friedman, HS, Kinney, TR, Chaffee, S, Stine, K, Falletta, JM, and Weinhold, KJ. "Management of human immunodeficiency virus-associated thrombocytopenia with intravenous gamma globulin." Am J Pediatr Hematol Oncol 9.4 (1987): 299-301.
PMID
2449828
Source
pubmed
Published In
American Journal of Pediatric Hematology/Oncology
Volume
9
Issue
4
Publish Date
1987
Start Page
299
End Page
301

Prospects for development of a vaccine against HTLV-III-related disorders.

Authors
Matthews, TJ; Lyerly, HK; Weinhold, KJ; Langlois, AJ; Rusche, J; Putney, SD; Gallo, RC; Bolognesi, DP
MLA Citation
Matthews, TJ, Lyerly, HK, Weinhold, KJ, Langlois, AJ, Rusche, J, Putney, SD, Gallo, RC, and Bolognesi, DP. "Prospects for development of a vaccine against HTLV-III-related disorders." AIDS Res Hum Retroviruses 3 Suppl 1 (1987): 197-206. (Review)
PMID
2825738
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
3 Suppl 1
Publish Date
1987
Start Page
197
End Page
206
DOI
10.1089/aid.1987.3.197

Transmission of HIV by antigen presenting cells during T-cell activation: prevention by 3'-azido-3'-deoxythymidine.

Tetanus toxoid (TT) reactive CD4+ cells were infected with HTLV-IIIB and exposed to TT at various times throughout a 7-day interval. Acute infection per se failed to produce overt cytopathology. However, exposure of infected cells to TT resulted in a rapid loss of cell viability, an increase in viral p24 expression, and a decline in T-cell blastogenesis. To determine whether HIV infection of antigen presenting cells (APC) could impact on T-cell activation, virus infected APC were utilized to present TT to responsive CD4+ cells. Use of infected APC produced effects similar to antigen stimulation of infected T-cells. These results suggest that the conditions of antigen presentation during T-cell activation may provide an excellent opportunity for virus transmission which may produce maximal immune dysfunction. However, preincubating antigen specific T-cells with the virostatic agent 3'-azido-3'-deoxythymidine (AZT) could prevent most of these effects.

Authors
Lyerly, HK; Cohen, OJ; Weinhold, KJ
MLA Citation
Lyerly, HK, Cohen, OJ, and Weinhold, KJ. "Transmission of HIV by antigen presenting cells during T-cell activation: prevention by 3'-azido-3'-deoxythymidine." AIDS Res Hum Retroviruses 3.1 (1987): 87-94.
PMID
3497654
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
3
Issue
1
Publish Date
1987
Start Page
87
End Page
94
DOI
10.1089/aid.1987.3.87

Anti-GP 120 antibodies from HIV seropositive individuals mediate broadly reactive anti-HIV ADCC.

Cytophilic antibodies which mediate antibody dependent cellular cytotoxicity (ADCC) against envelope antigens of human immunodeficiency virus (HIV) can be found in seropositive individuals. In these experiments, sera from a wide spectrum of HIV infected patients ranging from asymptomatic to overt acquired immunodeficiency syndrome (AIDS) were shown to contain high titers of antibodies that mediate ADCC. Not only did patient antibodies bind to surface expressed viral antigens and mediate ADCC against cells chronically infected with human T-lymphotropic virus type IIIB (HTLV-IIIB), but also against cells infected with the divergent HTLV-IIIRF2 and HTLV-IIIMN viral isolates. Similar results were obtained with target cells bearing purified GP 120 from HTLV-IIIB and HTLV-IIIRF2, indicating that a major portion of the activity was mediated by anti-GP 120 antibodies. Consistent with this was the ability to absorb most of the group-specific ADCC activity from the serum of an HIV infected individual using affinity columns bearing purified HTLV-IIIB GP 120. The finding that human antibodies reactive against the HIV envelope glycoprotein mediate ADCC against cells chronically infected with divergent strains of HIV will have important implications in designing rational approaches to passive and active immunotherapy.

Authors
Lyerly, HK; Reed, DL; Matthews, TJ; Langlois, AJ; Ahearne, PA; Petteway, SR; Weinhold, KJ
MLA Citation
Lyerly, HK, Reed, DL, Matthews, TJ, Langlois, AJ, Ahearne, PA, Petteway, SR, and Weinhold, KJ. "Anti-GP 120 antibodies from HIV seropositive individuals mediate broadly reactive anti-HIV ADCC." AIDS Res Hum Retroviruses 3.4 (1987): 409-422.
PMID
2833917
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
3
Issue
4
Publish Date
1987
Start Page
409
End Page
422
DOI
10.1089/aid.1987.3.409

Prospects for development of a vaccine against HIV-related disorders

Authors
Matthews, TJ; Lyerly, HK; Weinhold, KJ; Langlois, AJ; Putney, SD; Bolognesi, DP
MLA Citation
Matthews, TJ, Lyerly, HK, Weinhold, KJ, Langlois, AJ, Putney, SD, and Bolognesi, DP. "Prospects for development of a vaccine against HIV-related disorders." Clinical Immunology Newsletter 8.4 (1987): 49-52.
Source
scival
Published In
Clinical Immunology Newsletter
Volume
8
Issue
4
Publish Date
1987
Start Page
49
End Page
52

Augmentation of anti-HIV ADCC with interleukin-2

Authors
Lyerly, HK; Matthews, TJ; Aherne, PM; Langlois, AJ; Bolognesi, DP; Weinhold, KJ
MLA Citation
Lyerly, HK, Matthews, TJ, Aherne, PM, Langlois, AJ, Bolognesi, DP, and Weinhold, KJ. "Augmentation of anti-HIV ADCC with interleukin-2." Surgical Forum 38 (1987): 425-428.
Source
scival
Published In
Surgical Forum
Volume
38
Publish Date
1987
Start Page
425
End Page
428

TYPE SPECIFIC BINDING OF SURFACE EXPRESSED GP120 BY ANTI-GP120 SERUM

Authors
LYERLY, HK; WEINHOLD, KJ; MATTHEWS, TJ; PUTNEY, S; RUSCHE, J; LANGLOIS, AJ; BOLOGNESI, DP
MLA Citation
LYERLY, HK, WEINHOLD, KJ, MATTHEWS, TJ, PUTNEY, S, RUSCHE, J, LANGLOIS, AJ, and BOLOGNESI, DP. "TYPE SPECIFIC BINDING OF SURFACE EXPRESSED GP120 BY ANTI-GP120 SERUM." 1987.
Source
wos-lite
Published In
Journal of Cellular Biochemistry
Publish Date
1987
Start Page
73
End Page
73

HTLV-III/LAV-neutralizing antibodies to an E. coli-produced fragment of the virus envelope.

Immunization with either an Escherichia coli recombinant segment of the human T-cell lymphotropic virus (HTLV-III/LAV) envelope protein (gp 120) or with deglycosylated gp 120 envelope protein produced antibodies that neutralize HTLV-III/LAV infection in vitro. Virus neutralization titers of these antisera were equivalent to those obtained with purified native gp120 as immunogen. This localizes at least one class of neutralizing epitopes to the carboxyl-terminal half of the molecule. In addition, native gp120 prevented HTLV-III/LAV--mediated cell fusion, whereas the recombinant gp120 fragment did not. This shows that although glycosylation is not required for induction of neutralizing antibodies, it may be important for interaction with CD4, the virus receptor. A segment of the HTLV-III/LAV envelope produced in E. coli may be an important ingredient of a vaccine for acquired immune deficiency syndrome.

Authors
Putney, SD; Matthews, TJ; Robey, WG; Lynn, DL; Robert-Guroff, M; Mueller, WT; Langlois, AJ; Ghrayeb, J; Petteway, SR; Weinhold, KJ
MLA Citation
Putney, SD, Matthews, TJ, Robey, WG, Lynn, DL, Robert-Guroff, M, Mueller, WT, Langlois, AJ, Ghrayeb, J, Petteway, SR, and Weinhold, KJ. "HTLV-III/LAV-neutralizing antibodies to an E. coli-produced fragment of the virus envelope." Science 234.4782 (December 12, 1986): 1392-1395.
PMID
2431482
Source
pubmed
Published In
Science
Volume
234
Issue
4782
Publish Date
1986
Start Page
1392
End Page
1395

Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase.

The thymidine analog 3'-azido-3'-deoxythymidine (BW A509U, azidothymidine) can inhibit human immunodeficiency virus (HIV) replication effectively in the 50-500 nM range [Mitsuya, H., Weinhold, K. J., Furman, P. A., St. Clair, M. H., Nusinoff-Lehrman, S., Gallo, R. C., Bolognesi, D., Barry, D. W. & Broder, S. (1985) Proc. Natl. Acad. Sci. USA 82, 7096-7100]. In contrast, inhibition of the growth of uninfected human fibroblasts and lymphocytes has been observed only at concentrations above 1 mM. The nature of this selectivity was investigated. Azidothymidine anabolism to the 5'-mono-, di-, and -triphosphate derivatives was similar in uninfected and HIV-infected cells. The level of azidothymidine monophosphate was high, whereas the levels of the di- and triphosphate were low (less than or equal to 5 microM and less than or equal to 2 microM, respectively). Cytosolic thymidine kinase (EC 2.7.1.21) was responsible for phosphorylation of azidothymidine to its monophosphate. Purified thymidine kinase catalyzed the phosphorylations of thymidine and azidothymidine with apparent Km values of 2.9 microM and 3.0 microM. The maximal rate of phosphorylation with azidothymidine was equal to 60% of the rate with thymidine. Phosphorylation of azidothymidine monophosphate to the diphosphate also appeared to be catalyzed by a host-cell enzyme, thymidylate kinase (EC 2.7.4.9). The apparent Km value for azidothymidine monophosphate was 2-fold greater than the value for dTMP (8.6 microM vs. 4.1 microM), but the maximal phosphorylation rate was only 0.3% of the dTMP rate. These kinetic constants were consistent with the anabolism results and indicated that azidothymidine monophosphate is an alternative-substrate inhibitor of thymidylate kinase. This conclusion was reflected in the observation that cells incubated with azidothymidine had reduced intracellular levels of dTTP. IC50 (concentration of inhibitor that inhibits enzyme activity 50%) values were determined for azidothymidine triphosphate with HIV reverse transcriptase and with immortalized human lymphocyte (H9 cell) DNA polymerase alpha. Azidothymidine triphosphate competed about 100-fold better for the HIV reverse transcriptase than for the cellular DNA polymerase alpha. The results reported here suggest that azidothymidine is nonselectively phosphorylated but that the triphosphate derivative efficiently and selectively binds to the HIV reverse transcriptase. Incorporation of azidothymidylate into a growing DNA strand should terminate DNA elongation and thus inhibit DNA synthesis.

Authors
Furman, PA; Fyfe, JA; St Clair, MH; Weinhold, K; Rideout, JL; Freeman, GA; Lehrman, SN; Bolognesi, DP; Broder, S; Mitsuya, H
MLA Citation
Furman, PA, Fyfe, JA, St Clair, MH, Weinhold, K, Rideout, JL, Freeman, GA, Lehrman, SN, Bolognesi, DP, Broder, S, and Mitsuya, H. "Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase." Proc Natl Acad Sci U S A 83.21 (November 1986): 8333-8337.
PMID
2430286
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
83
Issue
21
Publish Date
1986
Start Page
8333
End Page
8337

ADMINISTRATION OF 3'-AZIDO-3'-DEOXYTHYMIDINE, AN INHIBITOR OF HTLV-III/LAV REPLICATION, TO PATIENTS WITH AIDS OR AIDS-RELATED COMPLEX

Authors
YARCHOAN, R; KLECKER, RW; WEINHOLD, KJ; MARKHAM, PD; DURACK, DT; GELMANN, E; LEHRMAN, SN; KIRK, LE; DRUCKER, J; BARRY, DW; MITSUYA, H; BOLOGNESI, DP; COLLINS, JM; MYERS, CE; BRODER, S
MLA Citation
YARCHOAN, R, KLECKER, RW, WEINHOLD, KJ, MARKHAM, PD, DURACK, DT, GELMANN, E, LEHRMAN, SN, KIRK, LE, DRUCKER, J, BARRY, DW, MITSUYA, H, BOLOGNESI, DP, COLLINS, JM, MYERS, CE, and BRODER, S. "ADMINISTRATION OF 3'-AZIDO-3'-DEOXYTHYMIDINE, AN INHIBITOR OF HTLV-III/LAV REPLICATION, TO PATIENTS WITH AIDS OR AIDS-RELATED COMPLEX." April 1986.
Source
wos-lite
Published In
Clinical Research
Volume
34
Issue
2
Publish Date
1986
Start Page
A511
End Page
A511

Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex.

In a 6-week clinical trial 4 dose regimens of 3'-azido-3'-deoxythymidine (AZT), a thymidine analogue with potent anti-viral activity against HTLV-III in vitro, were examined in 19 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). AZT was given intravenously for 2 weeks, then orally for 4 weeks at twice the intravenous dose. AZT was well absorbed from the gut and crossed the blood-brain barrier. Therapeutic levels were maintained with 5 mg given intravenously or 10 mg given orally every 4 h. Treatment was not limited by side-effects, the commonest of which were headaches and depression of white-cell counts. 15 of the 19 patients had increases in their numbers of circulating helper-inducer T lymphocytes (p less than 0.001) during therapy, 6 who were anergic at entry showed positive delayed type hypersensitivity skin test reactions during treatment, 2 had clearance of chronic fungal nailbed infections without specific anti-fungal therapy, 6 had other evidence of clinical improvement, and the group as a whole had a weight gain of 2.2 kg. Also, with the highest dose regimen cultures of peripheral blood mononuclear cells for HTLV III became negative.

Authors
Yarchoan, R; Klecker, RW; Weinhold, KJ; Markham, PD; Lyerly, HK; Durack, DT; Gelmann, E; Lehrman, SN; Blum, RM; Barry, DW
MLA Citation
Yarchoan, R, Klecker, RW, Weinhold, KJ, Markham, PD, Lyerly, HK, Durack, DT, Gelmann, E, Lehrman, SN, Blum, RM, and Barry, DW. "Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex." Lancet 1.8481 (March 15, 1986): 575-580.
PMID
2869302
Source
pubmed
Published In
The Lancet
Volume
1
Issue
8481
Publish Date
1986
Start Page
575
End Page
580

HTLV-III seroconversion associated with heat-treated factor VIII concentrate.

Authors
White, GC; Matthews, TJ; Weinhold, KJ; Haynes, BF; Cromartie, HL; McMillan, CW; Bolognesi, DP
MLA Citation
White, GC, Matthews, TJ, Weinhold, KJ, Haynes, BF, Cromartie, HL, McMillan, CW, and Bolognesi, DP. "HTLV-III seroconversion associated with heat-treated factor VIII concentrate." Lancet 1.8481 (March 15, 1986): 611-612. (Letter)
PMID
2869318
Source
pubmed
Published In
The Lancet
Volume
1
Issue
8481
Publish Date
1986
Start Page
611
End Page
612

Properties of mouse leukemia viruses: XX. Variation of AKR substrains in response to antibody therapy

In previous reports in this series, we have demonstrated that treatment of young AKR mice with IgG prepared against the viral envelope glycoprotein suppresses the development of spontaneous leukemia. Moreover, animals exhibiting high anti-viral antibody titers can transfer protection to their offspring. In this report we have extended the studies to another strain of AKR mice and find that the ability to transfer protection to offspring was not obtained. Foster nursing experiments were therefore conducted and their outcomes are indicative that maternal factors may be responsible for this phenomenon. © 1986.

Authors
Schwarz, H; Thiel, H-J; Weinhold, K; Fischinger, P; Bolognesi, D; Schäfer, W
MLA Citation
Schwarz, H, Thiel, H-J, Weinhold, K, Fischinger, P, Bolognesi, D, and Schäfer, W. "Properties of mouse leukemia viruses: XX. Variation of AKR substrains in response to antibody therapy." Virology 150.1 (1986): 247-251.
PMID
3952985
Source
scival
Published In
Virology
Volume
150
Issue
1
Publish Date
1986
Start Page
247
End Page
251

Immunologic control of a retrovirus-associated murine adenocarcinoma. VII. Tumor cell destruction by macrophages and IgG2A.

The mechanism by which IgG2A from a syngeneic antitumor hyperimmune serum mediates destruction of target cells in the presence of thioglycollate-elicited peritoneal macrophages was investigated by using an in vitro assay system. Labeled tumor cells were found to exhibit a biphasic pattern of binding to the effector cells; this binding pattern was dependent on the presence of specific antibody. The initial binding phase produced no apparent changes in the target cell population. Target cells coated with specific antibody exhibited a similar early binding phase, but excess free antibody was required for the subsequent binding phase and its associated release of radiolabel and cell destruction. Several features of this process observed distinguished it from more conventional forms of antibody-dependent cell-mediated cytoxicity. These included 1) the preference for antibodies of the IgG2A isotype, 2) the association of cell destruction with the release of nuclear but not cytoplasmic label, and 3) the requirement of excess free antibody for target cell killing.

Authors
Langlois, AJ; Matthews, TJ; Weinhold, KJ; Bolognesi, DP
MLA Citation
Langlois, AJ, Matthews, TJ, Weinhold, KJ, and Bolognesi, DP. "Immunologic control of a retrovirus-associated murine adenocarcinoma. VII. Tumor cell destruction by macrophages and IgG2A." J Natl Cancer Inst 75.4 (October 1985): 709-715.
PMID
3862903
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
75
Issue
4
Publish Date
1985
Start Page
709
End Page
715

Immunologic control of a retrovirus-associated murine adenocarcinoma. VI. Augmentation of antibody-dependent killing following quantitative and qualitative changes in host peritoneal cells.

Attempts were made to augment the antibody-dependent killing of the ascitic AD755a tumor in vivo to protect C57BL/6J mice against the outgrowth of larger tumor burdens. The lethal dose for this tumor is less than 100 cells, and antibodies contained in a hyperimmune antitumor serum (HIS) were found to suppress the outgrowth of a maximum of about 5 X 10(5) cells. Thioglycollate injected ip increased the number of peritoneal macrophages, potential effectors for antibody-dependent cell-mediated cytotoxicity (ADCC), by tenfold to fortyfold and raised the maximum treatable tumor challenge (MTTC) to about 4 X 10(6) cells. By comparison, ip injection of Corynebacterium parvum increased the total peritoneal cell population by only twofold but raised the MTTC to about 20 X 10(6) cells. Neither agent alone had an effect on long-term survival, even at very low tumor inocula (1 X 10(3) cells). The protective HIS is known to contain tumor-binding antibodies in each of the IgG1, IgG2A, and IgG2B isotype fractions. Although the IgG2A fraction is far superior in vivo in the suppression of tumor outgrowth, the IgG2A fraction was also found to be most effective in combination with thioglycollate treatment in agreement with the observed preference of thioglycollate-elicited macrophages for this isotype in in vitro killing assays. In contrast following C. parvum treatment, all three isoptype fractions were equally suppressive to tumor outgrowth. A second major change following C. parvum treatment was that tumor cells precoated in vitro with antibodies were effectively eliminated in vivo. The same antibody-coated cells administered to thioglycollate-treated or unmanipulated animals were uniformly lethal even at much lower tumor doses. Taken together these results suggested a major qualitative change in the antibody-dependent tumor-killing process following C. parvum treatment. This change was most likely due to the C. parvum activation of highly lytic effector cells for ADCC, the identity of which was examined in an accompanying manuscript.

Authors
Matthews, TJ; Weinhold, KJ; Langlois, AJ; Bolognesi, DP
MLA Citation
Matthews, TJ, Weinhold, KJ, Langlois, AJ, and Bolognesi, DP. "Immunologic control of a retrovirus-associated murine adenocarcinoma. VI. Augmentation of antibody-dependent killing following quantitative and qualitative changes in host peritoneal cells." J Natl Cancer Inst 75.4 (October 1985): 703-708.
PMID
3862902
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
75
Issue
4
Publish Date
1985
Start Page
703
End Page
708

Immunologic control of a retrovirus-associated murine adenocarcinoma. VIII. Corynebacterium parvum-activated natural killer cells as potent antibody-dependent cell-mediated cytotoxicity effectors.

The antibody-dependent lytic activity of Corynebacterium parvum-induced peritoneal exudate cells was examined in vitro by utilizing AD755a tumor targets and a homologous anti-AD755a hyperimmune serum. Maximum antibody-dependent cell-mediated cytolysis (ADCC) of tumor targets was achieved within 4 hours of incubation. ADCC activity was found primarily in the plastic nonadherent cell population and was greatly enriched following removal of phagocytic cells by carbonyl iron. Phenotypically, the cells active in short-term ADCC were Qa-5+, ASGM-1+, Thy 1.2+, and NK 1.1+ and were unaffected by treatment with Lyt 1.2, Lyt 2.2, MAC-1, or I-Ab antibodies plus complement. Cells active in antibody-independent lysis of AD755a targets were phenotypically identical to antibody-dependent effectors. Although indicative of a natural killer (NK) cell phenotype, C. parvum-induced effectors differed from "spontaneous" splenic NK cells in their relative sensitivity to anti-Thy 1.2 as well as to anti-NK 1.1 treatment. Unlike the IgG2a-dependent lysis of AD755a-derived cells by inflammatory macrophages, all IgG isotypes of antiAD755a serum were equally effective in ADCC mediated by C. parvum NK cells. Finally, treatment of C. parvum-inoculated animals with anti-ASGM-1 serum eliminated in vitro NK activity and abrogated the in vivo therapeutic effects of hyperimmune serum. These findings, together with other correlations detailed herein, strongly suggested that C. parvum-activated NK cells appeared to represent a unique subset of NK cells that can serve as potent effectors in the antibody-dependent killing of AD755a tumor cells.

Authors
Weinhold, KJ; Bolognesi, DP; Matthews, TJ
MLA Citation
Weinhold, KJ, Bolognesi, DP, and Matthews, TJ. "Immunologic control of a retrovirus-associated murine adenocarcinoma. VIII. Corynebacterium parvum-activated natural killer cells as potent antibody-dependent cell-mediated cytotoxicity effectors." J Natl Cancer Inst 75.4 (October 1985): 717-724.
PMID
3862904
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
75
Issue
4
Publish Date
1985
Start Page
717
End Page
724

3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro.

The acquired immune deficiency syndrome (AIDS) is thought to result from infection of T cells by a pathogenic human retrovirus, human T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV). In this report, we describe the antiviral effects of a thymidine analogue,3'-azido-3'-deoxythymidine (BW A509U), which, as a triphosphate, inhibits the reverse transcriptase of HTLV-III/LAV. This agent blocks the expression of the p24 gag protein of HTLV-III/LAV in H9 cells following exposure to virus. The drug also inhibits the cytopathic effect of HTLV-IIIB (a virus derived from a pool of American patients) and HTLV-III/RF-II (an isolate obtained from a Haitian patient that differs by about 20% in the amino acid sequence of the envelope gene from several isolates of HTLV-III/LAV, including HTLV-IIIB, analyzed so far). 3'-Azido-3'-deoxythymidine also completely blocks viral replication as assessed by reverse transcriptase production in normal human peripheral blood mononuclear cells exposed to HTLV-IIIB. Finally, at concentrations of 3'-azido-3'-deoxythymidine that block the in vitro infectivity and cytopathic effect of HTLV-IIIB, the in vitro immune functions of normal T cells remain basically intact.

Authors
Mitsuya, H; Weinhold, KJ; Furman, PA; St Clair, MH; Lehrman, SN; Gallo, RC; Bolognesi, D; Barry, DW; Broder, S
MLA Citation
Mitsuya, H, Weinhold, KJ, Furman, PA, St Clair, MH, Lehrman, SN, Gallo, RC, Bolognesi, D, Barry, DW, and Broder, S. "3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro." Proc Natl Acad Sci U S A 82.20 (October 1985): 7096-7100.
PMID
2413459
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
82
Issue
20
Publish Date
1985
Start Page
7096
End Page
7100

Murine in vitro antigenic modification of tumor cells: effect on susceptibility to natural cell-mediated cytotoxicity.

A 3-methylcholanthrene [(MCA) CAS: 56-49-5]-induced fibrosarcoma cell line and its Friend murine leukemia virus-infected counterpart were assessed for their susceptibility to lysis by so-called "natural" effector cells in a series of 51Cr release assays. Detailed functional and phenotypic analysis of lytic effector cell populations from normal C57BL/6 mouse spleens revealed an identity most closely associated with natural cytotoxic cells. Neither tumor cell line was found to be sensitive to natural killer-mediated lysis. Additionally, virus infection of the MCA-induced fibrosarcoma cell line did not affect susceptibility to natural cell-mediated cytotoxicity.

Authors
Langweiler, M; Weinhold, KJ; Matthews, TJ; Bolognesi, DP
MLA Citation
Langweiler, M, Weinhold, KJ, Matthews, TJ, and Bolognesi, DP. "Murine in vitro antigenic modification of tumor cells: effect on susceptibility to natural cell-mediated cytotoxicity." J Natl Cancer Inst 74.3 (March 1985): 699-704.
PMID
2983140
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
74
Issue
3
Publish Date
1985
Start Page
699
End Page
704

[Stimulation of immunoreactivity against endogenous retroviruses and protection against leukemia in aged AKR mice after vaccination with antibodies to viral surface components. The role of antibodies to p15(E)].

Antibody against viral gp71 is effective therapeutically for high leukemic AKR mice if injected immediately after birth. No corresponding effect could be observed after inoculation later in life when the endogenous virus burden is already high. However, if antibody treatment was supplemented by the injection of p15(E) antibody, a therapeutic effect was observed even in older mice first treated at an age of 21/2 months. Those mice produced antibodies against viral surface proteins and appeared to be able to survive longer than control mice. Thus p15(E) antibody might be able to overcome retroviral associated immuno-deficiency. This therapy may have implications for the treatment of the apparently retroviral induced acquired immunodeficiency syndrome (AIDS) of man.

Authors
Schwarz, H; Thiel, HJ; Weinhold, KJ; Bolognesi, DP; Schäfer, W
MLA Citation
Schwarz, H, Thiel, HJ, Weinhold, KJ, Bolognesi, DP, and Schäfer, W. "[Stimulation of immunoreactivity against endogenous retroviruses and protection against leukemia in aged AKR mice after vaccination with antibodies to viral surface components. The role of antibodies to p15(E)]." Z Naturforsch C 39.11-12 (November 1984): 1199-1202.
PMID
6531950
Source
pubmed
Published In
Zeitschrift f�r Naturforschung. Section C: Biosciences
Volume
39
Issue
11-12
Publish Date
1984
Start Page
1199
End Page
1202

Properties of mouse leukemia viruses. XIX. Effective antibody therapy of AKR leukemia occurs independently of virus neutralization and produces long-term changes in the virus status of the thymus.

Administration of high-titered goat anti-FLV gp71 IgG to AKR mice during a narrow neonatal therapy "window" suppresses the early development of MuLV infectious cell centers (ICC) in spleen, thymus, and bone marrow. By 4-5 weeks of age ICC appear in spleen and marrow cell populations, rapidly increasing to plateau levels within 2 weeks in the absence of viremia. The thymus of treated animals remains devoid of detectable ICC throughout the 4-month period of testing. This pattern of ICC suppression occurs independently of virus neutralization as shown by the inability of F(ab')2 preparations, which retained neutralizing activity, to prevent early establishment of ICC. Immune IgG significantly decreases, but does not eliminate gp71 expression in all tissues tested. In control animals, ICC reside within a minor subpopulation of cortical, thymic T cells, whereas peripheral (i.e., splenic) ICC are totally devoid of conventional T cell, B cell, and macrophage phenotypic markers. Although thymocytes appear to be a major target of this antibody therapy, T-cell reactivity is not compromised.

Authors
Weinhold, KJ; Hüper, G; Matthews, TJ; Fischinger, PJ; Ihle, JN; Schwarz, H; Thiel, HJ; Schäfer, W; Bolognesi, DP
MLA Citation
Weinhold, KJ, Hüper, G, Matthews, TJ, Fischinger, PJ, Ihle, JN, Schwarz, H, Thiel, HJ, Schäfer, W, and Bolognesi, DP. "Properties of mouse leukemia viruses. XIX. Effective antibody therapy of AKR leukemia occurs independently of virus neutralization and produces long-term changes in the virus status of the thymus." Virology 135.1 (May 1984): 105-117.
PMID
6328742
Source
pubmed
Published In
Virology
Volume
135
Issue
1
Publish Date
1984
Start Page
105
End Page
117

Prospects for the immunological management of lethal tumors.

Authors
Iglehart, JD; Weinhold, KJ; Ward, EC; Matthews, TJ; Langlois, AJ; Schäfer, W; Bolognesi, DP
MLA Citation
Iglehart, JD, Weinhold, KJ, Ward, EC, Matthews, TJ, Langlois, AJ, Schäfer, W, and Bolognesi, DP. "Prospects for the immunological management of lethal tumors." Cancer Invest 1.5 (1983): 409-421. (Review)
PMID
6365274
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
1
Issue
5
Publish Date
1983
Start Page
409
End Page
421

DIFFERENTIAL TUMORICIDAL ACTIVITY OF MURINE IGG ISOTYPES ADMINISTERED EITHER ALONE OR IN COMBINATION WITH THIOGLYCOLLATE, OR C-PARVUM

Authors
MATTHEWS, TJ; LANGLOIS, AJ; WEINHOLD, KJ; BOLOGNESI, DP
MLA Citation
MATTHEWS, TJ, LANGLOIS, AJ, WEINHOLD, KJ, and BOLOGNESI, DP. "DIFFERENTIAL TUMORICIDAL ACTIVITY OF MURINE IGG ISOTYPES ADMINISTERED EITHER ALONE OR IN COMBINATION WITH THIOGLYCOLLATE, OR C-PARVUM." 1983.
Source
wos-lite
Published In
Hybridoma
Volume
2
Issue
1
Publish Date
1983
Start Page
120
End Page
120

Intracellular cleavage of an SSV coded gag-related protein.

Authors
Thiel, HJ; Weiland, F; Hafenrichter, R; Matthews, TJ; Weinhold, KJ
MLA Citation
Thiel, HJ, Weiland, F, Hafenrichter, R, Matthews, TJ, and Weinhold, KJ. "Intracellular cleavage of an SSV coded gag-related protein." Virology 123.1 (November 1982): 229-234.
PMID
6293193
Source
pubmed
Published In
Virology
Volume
123
Issue
1
Publish Date
1982
Start Page
229
End Page
234

Cross-reacting antigens on L5178Y cells which serve as targets for cytotoxic T-lymphocyte lysis during establishment of the tumor dormant state.

We have attempted to identify the antigen on L5178Y cells that is the target for peritoneal cytotoxic T-lymphocytes (CTL) generated in L5178Y-O (original) immunized and challenged DBA/2 mice during establishment of the L5178Y cell tumor dormant state. These CTL exhibited in vitro lytic activity against methylcholanthrene-induced L5178Y and P815Y cells as well as Gross virus-induced BALB/c cells but not against a variety of other H-2d-tumor cell lines. The pattern of susceptibility to cell-mediated immune cytolysis was identical to the pattern of AB-dependent complement-mediated cytolysis produced by a rabbit anti-L5178Y antiserum. Quantitative expression of surface H-2d determinants was not a limiting factor in tumor cell lysis by CTL. The degree of CTL lysis of the susceptible cell lines was directly related to the amount of tumor-associated antigen expressed on the cell surface. The pattern of in vitro susceptibility to CTL lysis correlated well with in vivo transplantation resistance. The L5178Y cell antigen target for both CTL and Ra-anti-L5178Y serum lysis is likely to be either an endogenous AKR ecotropic viral glycoprotein with a molecular weight of 71,000 or one of two cell surface determinants, at Mr 85,000 and 135,000. These higher-molecular-weight antigens are neither endogenous AKR ecotropic viral-induced nor murine leukemia virus group-specific precursor structural proteins but may be transformation antigens shared by the susceptible tumor cell lines.

Authors
Weinhold, KJ; Wheelock, EF
MLA Citation
Weinhold, KJ, and Wheelock, EF. "Cross-reacting antigens on L5178Y cells which serve as targets for cytotoxic T-lymphocyte lysis during establishment of the tumor dormant state." Cancer Res 42.9 (September 1982): 3607-3616.
PMID
6179603
Source
pubmed
Published In
Cancer Research
Volume
42
Issue
9
Publish Date
1982
Start Page
3607
End Page
3616

Immunotherapy of a murine leukemia virus-infected, chemically induced murine sarcoma with antiviral antibodies.

Many murine tumor models associated with murine leukemia virus(es) (MuLV) have been successfully treated by passive administration of antiviral antibodies. There is a large body of virus-negative tumors, however, which are lowly antigenic and thus refractory to such approaches. Therefore, an investigation was done for determination of whether such tumors could be rendered susceptible to passive serum therapy by introduction of MuLV antigens onto the tumor cell surface. For this purpose a 3-methylcholanthrene-induced fibro-sarcoma from inbred C57BL/6J mice was chosen. Following infection of the tumor in vitro with Friend murine leukemia virus (F-MuLV), the tumor was found to be susceptible to treatment with a high-titered heterologous anti-F-MuLV gp71 antiserum. The specificity of the treatment was determined by conduction of the therapy on the uninfected parental tumor, in which case there was no effect. In addition, therapy could be initiated at time points when demonstrable tumors were present and successfully treated animals were resistant to rechallenge with the infected tumor. Thus conversion of a lowly antigenic virus-negative tumor to an MuLV-positive antigenic tumor rendered such growths susceptible to immunologic management.

Authors
Ward, EC; Iglehart, JD; Weinhold, KJ; Bolognesi, DP
MLA Citation
Ward, EC, Iglehart, JD, Weinhold, KJ, and Bolognesi, DP. "Immunotherapy of a murine leukemia virus-infected, chemically induced murine sarcoma with antiviral antibodies." J Natl Cancer Inst 69.2 (August 1982): 509-515.
PMID
6955550
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
69
Issue
2
Publish Date
1982
Start Page
509
End Page
515

PROPERTIES OF MOUSE LEUKEMIA VIRUSES .18. EFFECTIVE TREATMENT OF AKR LEUKEMIA WITH ANTIBODY TO GP71 ELIMINATES THE NEONATAL BURST OF ECOTROPIC AKR VIRUS PRODUCING CELLS

Authors
FISCHINGER, PJ; DUNLOP, NM; SCHWARZ, H; IHLE, JN; WEINHOLD, K; BOLOGNESI, DP; SCHAFER, W
MLA Citation
FISCHINGER, PJ, DUNLOP, NM, SCHWARZ, H, IHLE, JN, WEINHOLD, K, BOLOGNESI, DP, and SCHAFER, W. "PROPERTIES OF MOUSE LEUKEMIA VIRUSES .18. EFFECTIVE TREATMENT OF AKR LEUKEMIA WITH ANTIBODY TO GP71 ELIMINATES THE NEONATAL BURST OF ECOTROPIC AKR VIRUS PRODUCING CELLS." VIROLOGY 119.1 (1982): 68-81.
PMID
6280386
Source
wos-lite
Published In
Virology
Volume
119
Issue
1
Publish Date
1982
Start Page
68
End Page
81
DOI
10.1016/0042-6822(82)90066-6

ANTIGENS IN NON PRODUCER CELLS AFTER TRANSFORMATION BY A PRIMATE RETROVIRUS, THE SIMIAN SARCOMA-VIRUS (SSV)

Authors
THIEL, HJ; MATTHEWS, TJ; WEINHOLD, KJ
MLA Citation
THIEL, HJ, MATTHEWS, TJ, and WEINHOLD, KJ. "ANTIGENS IN NON PRODUCER CELLS AFTER TRANSFORMATION BY A PRIMATE RETROVIRUS, THE SIMIAN SARCOMA-VIRUS (SSV)." 1982.
Source
wos-lite
Published In
Zentralblatt fur Bakteriologie, Mikrobiologie und Hygiene. 1. Abt. Originale A, Medizinische Mikrobiologie, Infektionskrankheiten und Parasitologie = International journal of microbiology and hygiene. A, Medical microbiology, infectious...
Volume
253
Issue
1
Publish Date
1982
Start Page
39
End Page
39

Identification of a 20,000-dalton protein in SSV-transformed nonproducer cells.

Authors
Thiel, HJ; Matthews, TJ; Weinhold, KJ; Broughton, EM
MLA Citation
Thiel, HJ, Matthews, TJ, Weinhold, KJ, and Broughton, EM. "Identification of a 20,000-dalton protein in SSV-transformed nonproducer cells." Virology 115.2 (December 1981): 401-405.
PMID
6274092
Source
pubmed
Published In
Virology
Volume
115
Issue
2
Publish Date
1981
Start Page
401
End Page
405

Clonal isolate of the simian sarcoma virus codes for a Gag-related 65,000-dalton protein.

Authors
Matthews, TJ; Broughton, EM; Weinhold, KJ; Bolognesi, DP; Graf, T; Beug, H
MLA Citation
Matthews, TJ, Broughton, EM, Weinhold, KJ, Bolognesi, DP, Graf, T, and Beug, H. "Clonal isolate of the simian sarcoma virus codes for a Gag-related 65,000-dalton protein." Virology 114.1 (October 15, 1981): 124-131.
PMID
6269281
Source
pubmed
Published In
Virology
Volume
114
Issue
1
Publish Date
1981
Start Page
124
End Page
131

In vivo antigenic modification of tumor cells. III. Metastatic thymic lymphoma specifically infected by thymotropic retrovirus.

Tissue distribution of radiation leukemia virus (RadLV) was examined after its inoculation into normal C57BL/6J (B6) mice, B6 mice bearing a transplantable, non-virus-producing thymic lymphoma (RL12-NP), and B6 mice bearing a transplanted non-virus producing, Harvey murine sarcoma virus-transformed fibrosarcoma. Virus expression was determined by competition radioimmunoassay for murine leukemia virus (MuLV) p30 (predominant group-reactive antigen of MuLV) and for RadLV p12 (a highly type-specific MuLV polypeptide) and by membrane immunofluorescence for cell surface gp71 (predominant envelope glycoprotein of MuLV). Normal adult B6 mice were given three sequential iv injections of RadLV and were examined several times up to 200 days later for the appearance of neoplastic disease or expression of virion antigens. No clinical abnormalities were noted, and animals remained healthy for greater than 200 days. Significant levels of MuLV p30 and RadLV p12 were detected only in the thymuses. Organs and tumors from RL12-NP-inoculated animals contained low or nondetectable levels of virion antigens. Inoculation of mice with RL12-Rad, a cell line derived by in vitro infection of RL12-NP cells with RadLV, produced widespread, discrete metastatic tumors and infiltrated the lymphoid organs of B6 mice in a pattern identical to that observed after administration of RL12-NP cells. Lymphoid organs of RL12-Rad-inoculated animals expressed variable levels of virion antigens reflecting differences in the extent of tumor cell infiltration as opposed to virus spread from tumor to host cells. Administration of infectious RadLV systemically into RL12-NP tumor-bearing animals converted these tumors to viron antigen expressors with levels in superinfected tumors equivalent to those found in RL12-Rad-induced tumors. Infection was highly selective, and host tissues were minimally contaminated by the inoculated virus. Part of this selectivity was explained by the thymotropic property of RadLV. A rapidly dividing murine fibrosarcoma was not infected by RadLV, but this same non-virus-expressing tumor could be infected by common fibrotropic MuLV isolates.

Authors
Iglehart, JD; Weinhold, KJ; Huper, G; Thiel, K; Bolognesi, DP
MLA Citation
Iglehart, JD, Weinhold, KJ, Huper, G, Thiel, K, and Bolognesi, DP. "In vivo antigenic modification of tumor cells. III. Metastatic thymic lymphoma specifically infected by thymotropic retrovirus." J Natl Cancer Inst 67.1 (July 1981): 123-130.
PMID
6265678
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
67
Issue
1
Publish Date
1981
Start Page
123
End Page
130

The tumor dormant state.

Authors
Wheelock, EF; Weinhold, KJ; Levich, J
MLA Citation
Wheelock, EF, Weinhold, KJ, and Levich, J. "The tumor dormant state." Adv Cancer Res 34 (1981): 107-140. (Review)
PMID
7025590
Source
pubmed
Published In
Advances in cancer research
Volume
34
Publish Date
1981
Start Page
107
End Page
140

In vivo lysis of L5178Y cells in the establishment of the tumor-dormant state in DBA/2 mice.

Authors
Wheelock, EF; Weinhold, KJ; Ingenito, GG; Goldstein, LT
MLA Citation
Wheelock, EF, Weinhold, KJ, Ingenito, GG, and Goldstein, LT. "In vivo lysis of L5178Y cells in the establishment of the tumor-dormant state in DBA/2 mice." J Immunol 124.4 (April 1980): 1642-1647.
PMID
7365237
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
124
Issue
4
Publish Date
1980
Start Page
1642
End Page
1647

Infection of artificial air pouches in the connective tissue of mice with Neisseria gonorrhoeae.

Artificial air pouches in the connective tissue of mice were evaluated as a means of studying Neisseria gonorrhoeae infections. Animals inoculated with type-1 N. gonorrhoeae cells developed an infection characterised by infiltration of polymorphonuclear leucocytes. Viable cocci could be recovered from the air pouches for up to 10 days after infection and intracellular cocci were evident in electronmicrographs within connective-tissue fibroblasts for at least 35 days, indicating that a persistent infection had been established. The mouse air pouch should be of value in the study of gonococcal and other infections.

Authors
Clark, JM; Weinhold, KJ
MLA Citation
Clark, JM, and Weinhold, KJ. "Infection of artificial air pouches in the connective tissue of mice with Neisseria gonorrhoeae." J Med Microbiol 12.2 (May 1979): 233-237.
PMID
110937
Source
pubmed
Published In
Journal of medical microbiology
Volume
12
Issue
2
Publish Date
1979
Start Page
233
End Page
237
DOI
10.1099/00222615-12-2-233

The tumor dormant state. Comparison of L5178Y cells used to establish dormancy with those that emerge after its termination.

The tumor dormant state established in L5178Y immunized and challenged mice is characterized by a prolonged period of clinical normalcy followed by rapid tumor outgrowth. The tumor cells which emerged after termination of the tumor dormant state had abnormal marker chromosomes identical to those in the L5178Y cells used in the original challenge inoculum, indicating that the emergent tumor cells were progeny of the challenge inoculum. Original and emergent L5178Y cells had equivalent in vivo growth rates, when inoculated into normal DBA/2 mice. The emergent L5178Y cells were less susceptible than original cells to in vitro lysis by tumor dormant PC. Original and emergent L5178Y cells expressed common tumor-associated target antigens for cytolytic effector cells. Both modulation and masking of these target antigens were ruled out as mechanisms for decreased susceptibility to cell-mediated cytolysis. Immunofluorescence revealed heterogeneity in tumor-associated antigen expression within both original and emergent cell populations, with a decreased intensity of staining in the emergent population. Both populations were equally susceptible to lysis by alloimmune cells, alloantiserum, and anti-Thy 1.2 serum, but emergent cells were less susceptible to lysis by serum directed against L5178Y TAA. Quantitative absorption revealed that the emergent L5178Y cells expressed eightfold less serologically detectable TAA than the original cells. These findings indicate that the host immune response developing during establishment of the tumor dormant state selects a stable tumor cell subpopulation which expresses decreased amounts of surface tumor-associated target antigens.

Authors
Weinhold, KJ; Miller, DA; Wheelock, EF
MLA Citation
Weinhold, KJ, Miller, DA, and Wheelock, EF. "The tumor dormant state. Comparison of L5178Y cells used to establish dormancy with those that emerge after its termination." J Exp Med 149.3 (March 1, 1979): 745-757.
PMID
429962
Source
pubmed
Published In
The Journal of Experimental Medicine
Volume
149
Issue
3
Publish Date
1979
Start Page
745
End Page
757

The tumor dormant state. Quantitation of L5178Y cells and host immune responses during the establishment and course of dormancy in syngeneic DBA/2 mice.

Subcutaneous implantation of DBA/2-derived L5178Y cells into DBA/2 mice followed 10 d later by nodule excision protected 100% of mice from the rapid outgrowth of an intraperitoneal challenge of L5178Y cells given 7 d postexcision. Challenged mice remained clinically normal for 48--250 d before onset of an ultimately fatal tumor outgrowth. The numbers of L5178Y cells in the peritoneal cavity increased logarithmically for 4 d after challenge and then declined to low but detectable levels which persisted throughout the clinically normal period. Cells active in 18-h in vitro cytolytic assays against 51Cr-labeled L5178Y target cells were found in the peritoneal cavity. The effector cells were determined to be Thy1.2 positive. Their activity was tumor specific and reached peak levels 4 d after tumor challenge and then gradually declined to undectable levels during the following 70 d. Tumor emergence occurred most frequently during the period when CMC activity was no longer demonstrable in the remaining clinically normal mice. A transient peak of low level cytophilic antitumor antibody was detected about 30 d after tumor cell challenge. The temporal associations between the numbers of tumor cells and the levels of cell-mediated lysis against L5178Y cells indicate the importance of the cell-mediated cytolysis response in limiting initial tumor outgrowth and suggest its role as one of the factors responsible for long-term tumor suppression during tumor dormancy.

Authors
Weinhold, KJ; Goldstein, LT; Wheelock, EF
MLA Citation
Weinhold, KJ, Goldstein, LT, and Wheelock, EF. "The tumor dormant state. Quantitation of L5178Y cells and host immune responses during the establishment and course of dormancy in syngeneic DBA/2 mice." J Exp Med 149.3 (March 1, 1979): 732-744.
PMID
311815
Source
pubmed
Published In
The Journal of Experimental Medicine
Volume
149
Issue
3
Publish Date
1979
Start Page
732
End Page
744

IMMUNOLOGICAL MECHANISMS INVOLVED IN ESTABLISHMENT AND MAINTENANCE OF TUMOR DORMANT STATE

Authors
WEINHOLD, KJ; WHEELOCK, EF
MLA Citation
WEINHOLD, KJ, and WHEELOCK, EF. "IMMUNOLOGICAL MECHANISMS INVOLVED IN ESTABLISHMENT AND MAINTENANCE OF TUMOR DORMANT STATE." 1978.
Source
wos-lite
Published In
Proceedings of the Annual Meeting- American Association for Cancer Research
Volume
19
Issue
MAR
Publish Date
1978
Start Page
95
End Page
95

IMMUNOLOGICAL BASIS OF TUMOR DORMANCY IN MICE

Authors
WEINHOLD, KJ; GENOVESI, E; MARX, PA; WHEELOCK, EF
MLA Citation
WEINHOLD, KJ, GENOVESI, E, MARX, PA, and WHEELOCK, EF. "IMMUNOLOGICAL BASIS OF TUMOR DORMANCY IN MICE." 1978.
Source
wos-lite
Published In
The FASEB Journal
Volume
37
Issue
6
Publish Date
1978
Start Page
1280
End Page
1280

Tumour-dormant states established with L5178Y lymphoma cells in immunised syngeneic murine hosts.

Authors
Weinhold, KJ; Goldstein, LT; Wheelock, EF
MLA Citation
Weinhold, KJ, Goldstein, LT, and Wheelock, EF. "Tumour-dormant states established with L5178Y lymphoma cells in immunised syngeneic murine hosts." Nature 270.5632 (November 3, 1977): 59-61.
PMID
927518
Source
pubmed
Published In
Nature
Volume
270
Issue
5632
Publish Date
1977
Start Page
59
End Page
61

MURINE MODELS OF TUMOR DORMANCY

Authors
WHEELOCK, EF; CARNEY, WP; WEINHOLD, KJ
MLA Citation
WHEELOCK, EF, CARNEY, WP, and WEINHOLD, KJ. "MURINE MODELS OF TUMOR DORMANCY." 1977.
Source
wos-lite
Published In
RES Journal of the Reticuloendothelial Society
Volume
22
Publish Date
1977
Start Page
A58
End Page
A58
Show More

Research Areas:

  • AIDS Vaccines
  • Acquired Immunodeficiency Syndrome
  • Administration, Oral
  • African Americans
  • Age Factors
  • Aged
  • Aging
  • Algorithms
  • Amino Acid Sequence
  • Antibodies
  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Antibody-Dependent Cell Cytotoxicity
  • Antigen Presentation
  • Antigen-Presenting Cells
  • Antigens, CD
  • Antigens, CD4
  • Antigens, CD8
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Neoplasm
  • Antigens, Surface
  • Antiretroviral Therapy, Highly Active
  • Antiviral Agents
  • Autoimmunity
  • Automation, Laboratory
  • Avipoxvirus
  • B-Cell Activating Factor
  • Binding Sites, Antibody
  • Binding, Competitive
  • Bone Marrow
  • Bone Marrow Cells
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Canada
  • Canarypox virus
  • Carbohydrate Metabolism
  • Case-Control Studies
  • Cell Count
  • Cell Proliferation
  • Cell Separation
  • Cell Transformation, Neoplastic
  • Chemokines
  • Chemotherapy, Cancer, Regional Perfusion
  • Child, Preschool
  • Chromium
  • Clinical Trials as Topic
  • Clone Cells
  • Coculture Techniques
  • Cohort Studies
  • Combined Modality Therapy
  • Connective Tissue
  • Cross Reactions
  • Cytokines
  • Cytomegalovirus Infections
  • Cytopathogenic Effect, Viral
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic
  • DNA Primers
  • DNA, Viral
  • DNA-Directed DNA Polymerase
  • Deltaretrovirus
  • Dendritic Cells
  • Disease Progression
  • Diseases
  • Dose-Response Relationship, Immunologic
  • Double-Blind Method
  • Down-Regulation
  • Drug Resistance, Viral
  • Enzyme-Linked Immunosorbent Assay
  • Epitope Mapping
  • Epitopes
  • Epitopes, T-Lymphocyte
  • European Continental Ancestry Group
  • Evolution, Molecular
  • Fas Ligand Protein
  • Female
  • Flow Cytometry
  • Fluoresceins
  • Fluorescent Antibody Technique
  • Follow-Up Studies
  • Freund's Adjuvant
  • Gene Expression
  • Gene Expression Regulation
  • Gene Products, gag
  • Gene Rearrangement, T-Lymphocyte
  • Genes, Viral
  • Genome, Viral
  • Goats
  • Gonorrhea
  • Grading
  • Granzymes
  • Guideline Adherence
  • HIV
  • HIV Antibodies
  • HIV Antigens
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp160
  • HIV Envelope Protein gp41
  • HIV Infections
  • HIV Long Terminal Repeat
  • HIV Reverse Transcriptase
  • HIV Seronegativity
  • HIV Seropositivity
  • HIV-1
  • HLA-B27 Antigen
  • Haplorhini
  • Hematopoietic Stem Cells
  • Hemocyanin
  • Hemophilia A
  • High-Throughput Screening Assays
  • Histocompatibility Antigens Class I
  • Humans
  • Immune Evasion
  • Immune Sera
  • Immune System
  • Immune Tolerance
  • Immunity
  • Immunity, Innate
  • Immunity, Mucosal
  • Immunization
  • Immunization Schedule
  • Immunization, Secondary
  • Immunoblotting
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunohistochemistry
  • Immunologic Deficiency Syndromes
  • Immunologic Memory
  • Immunosuppressive Agents
  • In Situ Hybridization
  • Inflammation Mediators
  • Infusions, Parenteral
  • Interferon-gamma
  • Interleukin-7
  • International Cooperation
  • Intestinal Absorption
  • Isoantigens
  • Killer Cells, Natural
  • Laboratories
  • Leukocyte Count
  • Leukocytes, Mononuclear
  • Lymphocyte Activation
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Lymphocyte Subsets
  • Lymphocytes
  • Lymphoma
  • Macrophages
  • Major Histocompatibility Complex
  • Male
  • Melanoma
  • Melphalan
  • Mice
  • Mice, Inbred C3H
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Myasthenia Gravis
  • Neisseria gonorrhoeae
  • Neoplasm Proteins
  • Neoplasm Transplantation
  • Neoplasms
  • Neuroblastoma
  • Neutralization Tests
  • Normal Distribution
  • Observer Variation
  • Pan troglodytes
  • Pancreas Transplantation
  • Peptide Fragments
  • Peptide Mapping
  • Peptides
  • Phagocytosis
  • Phenotype
  • Phosphoproteins
  • Phosphorylation
  • Pilot Projects
  • Plasmapheresis
  • Pneumonia, Pneumocystis
  • Polymerase Chain Reaction
  • Prognosis
  • Program Development
  • Program Evaluation
  • Prospective Studies
  • Protein Binding
  • Protein Processing, Post-Translational
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-fyn
  • Quality Control
  • Quality Improvement
  • Quality Indicators, Health Care
  • RNA
  • RNA-Directed DNA Polymerase
  • Rabbits
  • Rabies Vaccines
  • Rats
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Fc
  • Receptors, IgG
  • Receptors, Tumor Necrosis Factor, Type II
  • Recombinant Proteins
  • Reference Values
  • Regression Analysis
  • Remission Induction
  • Reproducibility of Results
  • Retrospective Studies
  • Retroviridae
  • Retroviridae Infections
  • Retroviridae Proteins
  • Reverse Transcriptase Inhibitors
  • Risk Factors
  • SAIDS Vaccines
  • Sarcoma, Kaposi
  • Sequence Analysis, Protein
  • Sequence Homology, Amino Acid
  • Sex Factors
  • Sexual Behavior
  • Sexually Transmitted Diseases
  • Signal Transduction
  • Simian Acquired Immunodeficiency Syndrome
  • Simian immunodeficiency virus
  • Skin Neoplasms
  • Specimen Handling
  • Standardization
  • Stem Cells
  • Substrate Specificity
  • Suppressor Factors, Immunologic
  • Surface Properties
  • Survival Rate
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocyte Subsets
  • T-Lymphocytes
  • T-Lymphocytes, Cytotoxic
  • T-Lymphocytes, Helper-Inducer
  • TNF-Related Apoptosis-Inducing Ligand
  • Thymidine
  • Thymidine Monophosphate
  • Thymine Nucleotides
  • Tissue Distribution
  • Transcription, Genetic
  • Transduction, Genetic
  • Transplantation, Homologous
  • Treatment Outcome
  • Trinidad and Tobago
  • Tritium
  • Tumor Cells, Cultured
  • Tumor Virus Infections
  • United States
  • Vaccination
  • Vaccines, DNA
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • Vaccinia virus
  • Veterans
  • Viral Envelope Proteins
  • Viral Load
  • Viral Proteins
  • Viremia
  • Virion
  • Virus Replication
  • Young Adult
  • ZAP-70 Protein-Tyrosine Kinase
  • Zidovudine
  • env Gene Products, Human Immunodeficiency Virus
  • src-Family Kinases