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Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120
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 sa...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693417/ https://www.ncbi.nlm.nih.gov/pubmed/29149197 http://dx.doi.org/10.1371/journal.pone.0185959 |
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author | deCamp, Allan C. Rolland, Morgane Edlefsen, Paul T. Sanders-Buell, Eric Hall, Breana Magaret, Craig A. Fiore-Gartland, Andrew J. Juraska, Michal Carpp, Lindsay N. Karuna, Shelly T. Bose, Meera LePore, Steven Miller, Shana O'Sullivan, Annemarie Poltavee, Kultida Bai, Hongjun Dommaraju, Kalpana Zhao, Hong Wong, Kim Chen, Lennie Ahmed, Hasan Goodman, Derrick Tay, Matthew Z. Gottardo, Raphael Koup, Richard A. Bailer, Robert Mascola, John R. Graham, Barney S. Roederer, Mario O’Connell, Robert J. Michael, Nelson L. Robb, Merlin L. Adams, Elizabeth D’Souza, Patricia Kublin, James Corey, Lawrence Geraghty, Daniel E. Frahm, Nicole Tomaras, Georgia D. McElrath, M. Juliana Frenkel, Lisa Styrchak, Sheila Tovanabutra, Sodsai Sobieszczyk, Magdalena E. Hammer, Scott M. Kim, Jerome H. Mullins, James I. Gilbert, Peter B. |
author_facet | deCamp, Allan C. Rolland, Morgane Edlefsen, Paul T. Sanders-Buell, Eric Hall, Breana Magaret, Craig A. Fiore-Gartland, Andrew J. Juraska, Michal Carpp, Lindsay N. Karuna, Shelly T. Bose, Meera LePore, Steven Miller, Shana O'Sullivan, Annemarie Poltavee, Kultida Bai, Hongjun Dommaraju, Kalpana Zhao, Hong Wong, Kim Chen, Lennie Ahmed, Hasan Goodman, Derrick Tay, Matthew Z. Gottardo, Raphael Koup, Richard A. Bailer, Robert Mascola, John R. Graham, Barney S. Roederer, Mario O’Connell, Robert J. Michael, Nelson L. Robb, Merlin L. Adams, Elizabeth D’Souza, Patricia Kublin, James Corey, Lawrence Geraghty, Daniel E. Frahm, Nicole Tomaras, Georgia D. McElrath, M. Juliana Frenkel, Lisa Styrchak, Sheila Tovanabutra, Sodsai Sobieszczyk, Magdalena E. Hammer, Scott M. Kim, Jerome H. Mullins, James I. Gilbert, Peter B. |
author_sort | deCamp, Allan C. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5693417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-56934172017-11-30 Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120 deCamp, Allan C. Rolland, Morgane Edlefsen, Paul T. Sanders-Buell, Eric Hall, Breana Magaret, Craig A. Fiore-Gartland, Andrew J. Juraska, Michal Carpp, Lindsay N. Karuna, Shelly T. Bose, Meera LePore, Steven Miller, Shana O'Sullivan, Annemarie Poltavee, Kultida Bai, Hongjun Dommaraju, Kalpana Zhao, Hong Wong, Kim Chen, Lennie Ahmed, Hasan Goodman, Derrick Tay, Matthew Z. Gottardo, Raphael Koup, Richard A. Bailer, Robert Mascola, John R. Graham, Barney S. Roederer, Mario O’Connell, Robert J. Michael, Nelson L. Robb, Merlin L. Adams, Elizabeth D’Souza, Patricia Kublin, James Corey, Lawrence Geraghty, Daniel E. Frahm, Nicole Tomaras, Georgia D. McElrath, M. Juliana Frenkel, Lisa Styrchak, Sheila Tovanabutra, Sodsai Sobieszczyk, Magdalena E. Hammer, Scott M. Kim, Jerome H. Mullins, James I. Gilbert, Peter B. PLoS One Research Article 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. Public Library of Science 2017-11-17 /pmc/articles/PMC5693417/ /pubmed/29149197 http://dx.doi.org/10.1371/journal.pone.0185959 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article deCamp, Allan C. Rolland, Morgane Edlefsen, Paul T. Sanders-Buell, Eric Hall, Breana Magaret, Craig A. Fiore-Gartland, Andrew J. Juraska, Michal Carpp, Lindsay N. Karuna, Shelly T. Bose, Meera LePore, Steven Miller, Shana O'Sullivan, Annemarie Poltavee, Kultida Bai, Hongjun Dommaraju, Kalpana Zhao, Hong Wong, Kim Chen, Lennie Ahmed, Hasan Goodman, Derrick Tay, Matthew Z. Gottardo, Raphael Koup, Richard A. Bailer, Robert Mascola, John R. Graham, Barney S. Roederer, Mario O’Connell, Robert J. Michael, Nelson L. Robb, Merlin L. Adams, Elizabeth D’Souza, Patricia Kublin, James Corey, Lawrence Geraghty, Daniel E. Frahm, Nicole Tomaras, Georgia D. McElrath, M. Juliana Frenkel, Lisa Styrchak, Sheila Tovanabutra, Sodsai Sobieszczyk, Magdalena E. Hammer, Scott M. Kim, Jerome H. Mullins, James I. Gilbert, Peter B. Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120 |
title | Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120 |
title_full | Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120 |
title_fullStr | Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120 |
title_full_unstemmed | Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120 |
title_short | Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120 |
title_sort | sieve analysis of breakthrough hiv-1 sequences in hvtn 505 identifies vaccine pressure targeting the cd4 binding site of env-gp120 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693417/ https://www.ncbi.nlm.nih.gov/pubmed/29149197 http://dx.doi.org/10.1371/journal.pone.0185959 |
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