Format

Send to

Choose Destination
Nature. 2014 Jan 23;505(7484):502-8. doi: 10.1038/nature12893. Epub 2013 Dec 18.

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

Author information

1
Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
2
SAIC-Frederick, Frederick National Laboratory, NIH, Frederick, Maryland 21702, USA.
3
1] Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA [2] George Washington University, Washington DC 20052, USA.
4
Los Alamos National Laboratories, Los Alamos, New Mexico 87545, USA.
5
Department of Surgery, Duke University, Durham, North Carolina 27710, USA.
6
1] Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA [2] Sanofi-Pasteur, Cambridge, Massachusetts 02139, USA.
7
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
8
Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA.
9
Fred Hutchison Cancer Research Center, Seattle, Washington 98109, USA.
10
Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland 20892, USA.
11
1] Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA [2].

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.

PMID:
24352234
PMCID:
PMC3946913
DOI:
10.1038/nature12893
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Secondary source ID, Grant support

Publication types

MeSH terms

Substances

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center