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PLoS One. 2017 Nov 17;12(11):e0185959. doi: 10.1371/journal.pone.0185959. eCollection 2017.

Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120.

Author information

1
Vaccine and Infectious Disease Division and Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
2
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
3
The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, United States of America.
4
Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
5
Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
6
Department of Biology, Emory University, Atlanta, Georgia, United States of America.
7
Duke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America.
8
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
9
Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
10
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
11
Department of Global Health, University of Washington, Seattle, Washington, United States of America.
12
Department of Medicine, University of Washington, Seattle, Washington, United States of America.
13
Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America.
14
Seattle Children's Research Institute, Seattle, Washington, United States of America.
15
Department of Pediatrics, University of Washington, Seattle, Washington, United States of America.
16
Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, United States of America.
17
International Vaccine Institute, Seoul, Korea.

Abstract

Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.

PMID:
29149197
PMCID:
PMC5693417
DOI:
10.1371/journal.pone.0185959
[Indexed for MEDLINE]
Free PMC Article
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