Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV.
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 articleSubject
AIDS VaccinesAmino 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
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https://hdl.handle.net/10161/14719Published Version (Please cite this version)
10.1038/nature12893Publication 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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Show full item recordScholars@Duke
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
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
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
Celia Crane LaBranche
Associate Professor Emeritus
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
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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