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

被引：122

作者：

Roederer, Mario ^{[1
]}

Keele, Brandon F. ^{[2
]}

Schmidt, Stephen D. ^{[1
]}

Mason, Rosemarie D. ^{[1
]}

Welles, Hugh C. ^{[1
,3
]}

Fischer, Will ^{[4
]}

Labranche, Celia ^{[5
]}

Foulds, Kathryn E. ^{[1
]}

Louder, Mark K. ^{[1
]}

Yang, Zhi-Yong ^{[1
]}

Todd, John-Paul M. ^{[1
]}

Buzby, Adam P. ^{[6
]}

Mach, Linh V. ^{[6
]}

Shen, Ling ^{[6
]}

Seaton, Kelly E. ^{[7
]}

Ward, Brandy M. ^{[5
]}

Bailer, Robert T. ^{[1
]}

Gottardo, Raphael ^{[8
]}

Gu, Wenjuan ^{[9
]}

Ferrari, Guido ^{[5
]}

Alam, S. Munir ^{[7
]}

Denny, Thomas N. ^{[7
]}

Montefiori, David C. ^{[5
]}

Tomaras, Georgia D. ^{[7
]}

Korber, Bette T. ^{[4
]}

Nason, Martha C. ^{[9
]}

Seder, Robert A. ^{[1
]}

Koup, Richard A. ^{[1
]}

Letvin, Norman L. ^{[6
]}

Rao, Srinivas S. ^{[1
]}

Nabel, Gary J. ^{[1
]}

Mascola, John R. ^{[1
]}

机构：

[1] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[2] NIH, SAIC Frederick, Frederick Natl Lab, Frederick, MD 21702 USA

[3] George Washington Univ, Washington, DC 20052 USA

[4] Los Alamos Natl Labs, Los Alamos, NM 87545 USA

[5] Duke Univ, Dept Surg, Durham, NC 27710 USA

[6] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02115 USA

[7] Duke Univ, Human Vaccine Inst, Durham, NC 27710 USA

[8] Fred Hutchison Canc Res Ctr, Seattle, WA 98109 USA

[9] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA

来源：

NATURE | 2014年 / 505卷 / 7484期

关键词：

SIMIAN IMMUNODEFICIENCY VIRUS; DOSE CHALLENGE EXPERIMENTS; NEUTRALIZING ANTIBODIES; RHESUS MACAQUES; CELL RESPONSES; EFFICACY TRIAL; INFECTION; BINDING; SIVSME660; PREVENTION;

D O I：

10.1038/nature12893

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：502 / +

页数：17

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