Publication Date:
2013-12-20
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946913/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946913/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- AI100645/AI/NIAID NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- HHSN27201100016C/PHS HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- Z99 AI999999/Intramural NIH HHS/ -- ZIA AI005019-12/Intramural NIH HHS/ -- England -- Nature. 2014 Jan 23;505(7484):502-8. doi: 10.1038/nature12893. Epub 2013 Dec 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA. ; SAIC-Frederick, Frederick National Laboratory, NIH, Frederick, Maryland 21702, USA. ; 1] Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA [2] George Washington University, Washington DC 20052, USA. ; Los Alamos National Laboratories, Los Alamos, New Mexico 87545, USA. ; Department of Surgery, Duke University, Durham, North Carolina 27710, USA. ; 1] Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA [2] Sanofi-Pasteur, Cambridge, Massachusetts 02139, USA. ; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA. ; Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA. ; Fred Hutchison Cancer Research Center, Seattle, Washington 98109, USA. ; Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland 20892, USA. ; 1] Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24352234" target="_blank"〉PubMed〈/a〉
Keywords:
AIDS Vaccines/*immunology
;
Amino Acid Sequence
;
Animals
;
Antibodies, Neutralizing/immunology
;
Disease Susceptibility/immunology
;
Female
;
Founder Effect
;
HIV Antibodies/immunology
;
HIV Infections/immunology/*prevention & control/*virology
;
HIV-1/chemistry/*immunology
;
Humans
;
Immune Evasion/immunology
;
Macaca mulatta
;
Male
;
Molecular Sequence Data
;
Phylogeny
;
Risk
;
SAIDS Vaccines/*immunology
;
Simian Acquired Immunodeficiency Syndrome/immunology/prevention &
;
control/virology
;
Simian Immunodeficiency Virus/chemistry/genetics/*immunology/physiology
;
env Gene Products, Human Immunodeficiency Virus/immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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