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Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV.

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Date
2014-01-23
Authors
Roederer, Mario
Keele, Brandon F
Schmidt, Stephen D
Mason, Rosemarie D
Welles, Hugh C
Fischer, Will
Labranche, Celia
Foulds, Kathryn E
Louder, Mark K
Yang, Zhi-Yong
Todd, John-Paul M
Buzby, Adam P
Mach, Linh V
Shen, Ling
Seaton, Kelly E
Ward, Brandy M
Bailer, Robert T
Gottardo, Raphael
Gu, Wenjuan
Ferrari, Guido
Alam, S Munir
Denny, Thomas N
Montefiori, David C
Tomaras, Georgia D
Korber, Bette T
Nason, Martha C
Seder, Robert A
Koup, Richard A
Letvin, Norman L
Rao, Srinivas S
Nabel, Gary J
Mascola, John R
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(32 total)
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Abstract
A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials.
Type
Journal article
Subject
AIDS Vaccines
Amino Acid Sequence
Animals
Antibodies, Neutralizing
Disease Susceptibility
Female
Founder Effect
HIV Antibodies
HIV Infections
HIV-1
Humans
Immune Evasion
Macaca mulatta
Male
Molecular Sequence Data
Phylogeny
Risk
SAIDS Vaccines
Simian Acquired Immunodeficiency Syndrome
Simian Immunodeficiency Virus
env Gene Products, Human Immunodeficiency Virus
Permalink
https://hdl.handle.net/10161/14719
Published Version (Please cite this version)
10.1038/nature12893
Publication Info
Roederer, Mario; Keele, Brandon F; Schmidt, Stephen D; Mason, Rosemarie D; Welles, Hugh C; Fischer, Will; ... Mascola, John R (2014). Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV. Nature, 505(7484). pp. 502-508. 10.1038/nature12893. Retrieved from https://hdl.handle.net/10161/14719.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Alam

S. Munir Alam

Professor in Medicine
Research Interests.  The Alam laboratory’s primary research is focused on understanding the biophysical properties of antigen-antibody binding and the molecular events of early B cell activation using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events for their activation. In the lon
Denny

Thomas Norton Denny

Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine Institute (DHVI) and the Center for HIV/AIDS Vaccine Immunology (CHAVI), and a Professor of Medicine in the Department of Medicine at Duke University Medical Center. He is also an Affiliate Member of the Duke Global Health Institute. He has recently been appointed to the Duke University Fuqua School of Business Health Sector Advisory Council. Previously, he was an Associate Professor of Pathology, Laboratory M
Ferrari

Guido Ferrari

Professor in Surgery
The activities of the Ferrari Laboratory are based on both independent basic research and immune monitoring studies. The research revolves around three main areas of interest: class I-mediated cytotoxic CD8+ T cell responses, antibody-dependent cellular cytotoxicity (ADCC), gene expression in NK and T cellular subsets upon infection with HIV-1. With continuous funding over the last 11 years from the NIH and Bill & Melinda Gates Foundation along with many other productive collaborations wi
LaBranche

Celia Crane LaBranche

Associate Professor Emeritus
Montefiori

David Charles Montefiori

Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for AIDS Vaccine Research and Development in the Department of Surgery, Division of Surgical Sciences, Duke University Medical Center. His major research interests are viral immunology and AIDS vaccine development, with a special emphasis on neutralizing antibodies. One of his highest priorities is to identify immunogens that generate broadly cross-reactive neutralizing antibodies for inclusion in HIV vaccines.  Many aspects of the
Tomaras

Georgia Doris Tomaras

Professor in Surgery
Dr. Georgia Tomaras is a tenured Professor of Surgery, Professor of Immunology, Professor of Molecular Genetics and Microbiology and is a Fellow of the American Academy of Microbiology (AAM) and a Fellow of the American Association for the Advancement of Science (AAAS).  Dr. Tomaras is Co-Director of the Center for Human Systems Immunology (CHSI) Duke University and Director of the Duke Center for AIDS Research (CFAR). Her national and international leadership roles i
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