Publication Date:
2012-09-11
Description:
The RV144 trial demonstrated 31% vaccine efficacy at preventing human immunodeficiency virus (HIV)-1 infection. Antibodies against the HIV-1 envelope variable loops 1 and 2 (Env V1 and V2) correlated inversely with infection risk. We proposed that vaccine-induced immune responses against V1/V2 would have a selective effect against, or sieve, HIV-1 breakthrough viruses. A total of 936 HIV-1 genome sequences from 44 vaccine and 66 placebo recipients were examined. We show that vaccine-induced immune responses were associated with two signatures in V2 at amino acid positions 169 and 181. Vaccine efficacy against viruses matching the vaccine at position 169 was 48% (confidence interval 18% to 66%; P = 0.0036), whereas vaccine efficacy against viruses mismatching the vaccine at position 181 was 78% (confidence interval 35% to 93%; P = 0.0028). Residue 169 is in a cationic glycosylated region recognized by broadly neutralizing and RV144-derived antibodies. The predicted distance between the two signature sites (21 +/- 7 A) and their match/mismatch dichotomy indicate that multiple factors may be involved in the protection observed in RV144. Genetic signatures of RV144 vaccination in V2 complement the finding of an association between high V1/V2-binding antibodies and reduced risk of HIV-1 acquisition, and provide evidence that vaccine-induced V2 responses plausibly had a role in the partial protection conferred by the RV144 regimen.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551291/" 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/PMC3551291/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rolland, Morgane -- Edlefsen, Paul T -- Larsen, Brendan B -- Tovanabutra, Sodsai -- Sanders-Buell, Eric -- Hertz, Tomer -- deCamp, Allan C -- Carrico, Chris -- Menis, Sergey -- Magaret, Craig A -- Ahmed, Hasan -- Juraska, Michal -- Chen, Lennie -- Konopa, Philip -- Nariya, Snehal -- Stoddard, Julia N -- Wong, Kim -- Zhao, Hong -- Deng, Wenjie -- Maust, Brandon S -- Bose, Meera -- Howell, Shana -- Bates, Adam -- Lazzaro, Michelle -- O'Sullivan, Annemarie -- Lei, Esther -- Bradfield, Andrea -- Ibitamuno, Grace -- Assawadarachai, Vatcharain -- O'Connell, Robert J -- deSouza, Mark S -- Nitayaphan, Sorachai -- Rerks-Ngarm, Supachai -- Robb, Merlin L -- McLellan, Jason S -- Georgiev, Ivelin -- Kwong, Peter D -- Carlson, Jonathan M -- Michael, Nelson L -- Schief, William R -- Gilbert, Peter B -- Mullins, James I -- Kim, Jerome H -- 2R37AI05465-10/AI/NIAID NIH HHS/ -- K25 AI087397/AI/NIAID NIH HHS/ -- R01 AI054165/AI/NIAID NIH HHS/ -- R37 AI054165/AI/NIAID NIH HHS/ -- UM1 AI068635/AI/NIAID NIH HHS/ -- Y01 AI2642-12/AI/NIAID NIH HHS/ -- Y1-AI-2642-12/AI/NIAID NIH HHS/ -- England -- Nature. 2012 Oct 18;490(7420):417-20. doi: 10.1038/nature11519. Epub 2012 Sep 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉US Military HIV Research Program, Silver Spring, Maryland 20910, USA. mrolland@hivresearch.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22960785" target="_blank"〉PubMed〈/a〉
Keywords:
AIDS Vaccines/adverse effects/*immunology
;
Genetic Predisposition to Disease
;
HIV Antibodies/immunology
;
HIV Infections/immunology/*prevention & control/*virology
;
HIV-1/*genetics/*immunology
;
Humans
;
Molecular Sequence Data
;
Phylogeny
;
Randomized Controlled Trials as Topic
;
Sequence Analysis, DNA
;
env Gene Products, Human Immunodeficiency Virus/*genetics/*immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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