Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env-V2
The RV144 trial demonstrated 31% vaccine efficacy (VE) at preventing HIV-1 infection1. Antibodies against the HIV-1 envelope variable loops 1 and 2 (V1/V2) domain correlated inversely with infection risk2. We hypothesized that vaccine-induced immune responses against V1/V2 would selectively impact,...
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| Format: | Online |
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2012
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551291/ |
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pubmed-3551291 |
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pubmed-35512912013-04-18 Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env-V2 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. Article The RV144 trial demonstrated 31% vaccine efficacy (VE) at preventing HIV-1 infection1. Antibodies against the HIV-1 envelope variable loops 1 and 2 (V1/V2) domain correlated inversely with infection risk2. We hypothesized that vaccine-induced immune responses against V1/V2 would selectively impact, or sieve, HIV-1 breakthrough viruses. 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 V1/V2 at amino-acid positions 169 and 181. VE against viruses matching the vaccine at position 169 was 48% (CI: 18 to 66%; p=0.0036), whereas VE against viruses mismatching the vaccine at position 181 was 78% (CI: 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 signatures sites (21±7 Å), and their match/mismatch dichotomy, suggest 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 played a role in the partial protection conferred by the RV144 regimen. 2012-09-10 2012-10-18 /pmc/articles/PMC3551291/ /pubmed/22960785 http://dx.doi.org/10.1038/nature11519 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
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Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
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. |
| spellingShingle |
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. Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env-V2 |
| author_facet |
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. |
| author_sort |
Rolland, Morgane |
| title |
Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env-V2 |
| title_short |
Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env-V2 |
| title_full |
Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env-V2 |
| title_fullStr |
Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env-V2 |
| title_full_unstemmed |
Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env-V2 |
| title_sort |
increased hiv-1 vaccine efficacy against viruses with genetic signatures in env-v2 |
| description |
The RV144 trial demonstrated 31% vaccine efficacy (VE) at preventing HIV-1 infection1. Antibodies against the HIV-1 envelope variable loops 1 and 2 (V1/V2) domain correlated inversely with infection risk2. We hypothesized that vaccine-induced immune responses against V1/V2 would selectively impact, or sieve, HIV-1 breakthrough viruses. 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 V1/V2 at amino-acid positions 169 and 181. VE against viruses matching the vaccine at position 169 was 48% (CI: 18 to 66%; p=0.0036), whereas VE against viruses mismatching the vaccine at position 181 was 78% (CI: 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 signatures sites (21±7 Å), and their match/mismatch dichotomy, suggest 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 played a role in the partial protection conferred by the RV144 regimen. |
| publishDate |
2012 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551291/ |
| _version_ |
1611948543686213632 |