Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial

被引：181

作者：

Rolland, Morgane ^{[1
]}

Tovanabutra, Sodsai ^{[2
]}

deCamp, Allan C. ^{[3
]}

Frahm, Nicole ^{[3
]}

Gilbert, Peter B. ^{[3
]}

Sanders-Buell, Eric ^{[2
]}

Heath, Laura ^{[1
]}

Magaret, Craig A. ^{[3
]}

Bose, Meera ^{[2
]}

Bradfield, Andrea ^{[2
]}

O'Sullivan, Annemarie ^{[2
]}

Crossler, Jacqueline ^{[2
]}

Jones, Teresa ^{[2
]}

Nau, Marty ^{[2
]}

Wong, Kim ^{[1
]}

Zhao, Hong ^{[1
]}

Raugi, Dana N. ^{[1
]}

Sorensen, Stephanie ^{[1
]}

Stoddard, Julia N. ^{[1
]}

Maust, Brandon S. ^{[1
]}

Deng, Wenjie ^{[1
]}

Hural, John ^{[3
]}

Dubey, Sheri ^{[4
]}

Michael, Nelson L. ^{[2
]}

Shiver, John ^{[4
]}

Corey, Lawrence ^{[3
]}

Li, Fusheng ^{[3
]}

Self, Steve G. ^{[3
]}

Kim, Jerome ^{[2
]}

Buchbinder, Susan ^{[5
]}

Casimiro, Danilo R. ^{[4
]}

Robertson, Michael N. ^{[4
]}

Duerr, Ann ^{[3
]}

McElrath, M. Juliana ^{[3
]}

McCutchan, Francine E. ^{[2
]}

Mullins, James I. ^{[1
]}

机构：

[1] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA

[2] US Mil HIV Res Program, Rockville, MD USA

[3] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98104 USA

[4] Merck Res Labs, West Point, PA USA

[5] San Francisco Dept Hlth, San Francisco, CA USA

来源：

NATURE MEDICINE | 2011年 / 17卷 / 03期

关键词：

T-LYMPHOCYTE RESPONSE; CELL RESPONSES; ESCAPE; PREDICTION; IMMUNITY; BINDING; GAG;

D O I：

10.1038/nm.2316

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We analyzed HIV-1 genome sequences from 68 newly infected volunteers in the STEP HIV-1 vaccine trial. To determine whether the vaccine exerted selective T cell pressure on breakthrough viruses, we identified potential T cell epitopes in the founder sequences and compared them to epitopes in the vaccine. We found greater distances to the vaccine sequence for sequences from vaccine recipients than from placebo recipients. The most significant signature site distinguishing vaccine from placebo recipients was Gag amino acid 84, a site encompassed by several epitopes contained in the vaccine and restricted by human leukocyte antigen (HLA) alleles common in the study cohort. Moreover, the extended divergence was confined to the vaccine components of the virus (HIV-1 Gag, Pol and Nef) and not found in other HIV-1 proteins. These results represent what is to our knowledge the first evidence of selective pressure from vaccine-induced T cell responses on HIV-1 infection in humans.

引用

页码：366 / U168

页数：7

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