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CD8 and CD4 Epitope Predictions in RV144: No Strong Evidence of a T-Cell Driven Sieve Effect in HIV-1 Breakthrough Sequences from Trial Participants

The modest protection afforded by the RV144 vaccine offers an opportunity to evaluate its mechanisms of protection. Differences between HIV-1 breakthrough viruses from vaccine and placebo recipients can be attributed to the RV144 vaccine as this was a randomized and double-blinded trial. CD8 and CD4...

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Autores principales: Dommaraju, Kalpana, Kijak, Gustavo, Carlson, Jonathan M., Larsen, Brendan B., Tovanabutra, Sodsai, Geraghty, Dan E., Deng, Wenjie, Maust, Brandon S., Edlefsen, Paul T., Sanders-Buell, Eric, Ratto-Kim, Silvia, deSouza, Mark S., Rerks-Ngarm, Supachai, Nitayaphan, Sorachai, Pitisuttihum, Punnee, Kaewkungwal, Jaranit, O'Connell, Robert J., Robb, Merlin L., Michael, Nelson L., Mullins, James I., Kim, Jerome H., Rolland, Morgane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211711/
https://www.ncbi.nlm.nih.gov/pubmed/25350851
http://dx.doi.org/10.1371/journal.pone.0111334
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author Dommaraju, Kalpana
Kijak, Gustavo
Carlson, Jonathan M.
Larsen, Brendan B.
Tovanabutra, Sodsai
Geraghty, Dan E.
Deng, Wenjie
Maust, Brandon S.
Edlefsen, Paul T.
Sanders-Buell, Eric
Ratto-Kim, Silvia
deSouza, Mark S.
Rerks-Ngarm, Supachai
Nitayaphan, Sorachai
Pitisuttihum, Punnee
Kaewkungwal, Jaranit
O'Connell, Robert J.
Robb, Merlin L.
Michael, Nelson L.
Mullins, James I.
Kim, Jerome H.
Rolland, Morgane
author_facet Dommaraju, Kalpana
Kijak, Gustavo
Carlson, Jonathan M.
Larsen, Brendan B.
Tovanabutra, Sodsai
Geraghty, Dan E.
Deng, Wenjie
Maust, Brandon S.
Edlefsen, Paul T.
Sanders-Buell, Eric
Ratto-Kim, Silvia
deSouza, Mark S.
Rerks-Ngarm, Supachai
Nitayaphan, Sorachai
Pitisuttihum, Punnee
Kaewkungwal, Jaranit
O'Connell, Robert J.
Robb, Merlin L.
Michael, Nelson L.
Mullins, James I.
Kim, Jerome H.
Rolland, Morgane
author_sort Dommaraju, Kalpana
collection PubMed
description The modest protection afforded by the RV144 vaccine offers an opportunity to evaluate its mechanisms of protection. Differences between HIV-1 breakthrough viruses from vaccine and placebo recipients can be attributed to the RV144 vaccine as this was a randomized and double-blinded trial. CD8 and CD4 T cell epitope repertoires were predicted in HIV-1 proteomes from 110 RV144 participants. Predicted Gag epitope repertoires were smaller in vaccine than in placebo recipients (p = 0.019). After comparing participant-derived epitopes to corresponding epitopes in the RV144 vaccine, the proportion of epitopes that could be matched differed depending on the protein conservation (only 36% of epitopes in Env vs 84–91% in Gag/Pol/Nef for CD8 predicted epitopes) or on vaccine insert subtype (55% against CRF01_AE vs 7% against subtype B). To compare predicted epitopes to the vaccine, we analyzed predicted binding affinity and evolutionary distance measurements. Comparisons between the vaccine and placebo arm did not reveal robust evidence for a T cell driven sieve effect, although some differences were noted in Env-V2 (0.022≤p-value≤0.231). The paucity of CD8 T cell responses identified following RV144 vaccination, with no evidence for V2 specificity, considered together both with the association of decreased infection risk in RV 144 participants with V-specific antibody responses and a V2 sieve effect, lead us to hypothesize that this sieve effect was not T cell specific. Overall, our results did not reveal a strong differential impact of vaccine-induced T cell responses among breakthrough infections in RV144 participants.
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spelling pubmed-42117112014-11-05 CD8 and CD4 Epitope Predictions in RV144: No Strong Evidence of a T-Cell Driven Sieve Effect in HIV-1 Breakthrough Sequences from Trial Participants Dommaraju, Kalpana Kijak, Gustavo Carlson, Jonathan M. Larsen, Brendan B. Tovanabutra, Sodsai Geraghty, Dan E. Deng, Wenjie Maust, Brandon S. Edlefsen, Paul T. Sanders-Buell, Eric Ratto-Kim, Silvia deSouza, Mark S. Rerks-Ngarm, Supachai Nitayaphan, Sorachai Pitisuttihum, Punnee Kaewkungwal, Jaranit O'Connell, Robert J. Robb, Merlin L. Michael, Nelson L. Mullins, James I. Kim, Jerome H. Rolland, Morgane PLoS One Research Article The modest protection afforded by the RV144 vaccine offers an opportunity to evaluate its mechanisms of protection. Differences between HIV-1 breakthrough viruses from vaccine and placebo recipients can be attributed to the RV144 vaccine as this was a randomized and double-blinded trial. CD8 and CD4 T cell epitope repertoires were predicted in HIV-1 proteomes from 110 RV144 participants. Predicted Gag epitope repertoires were smaller in vaccine than in placebo recipients (p = 0.019). After comparing participant-derived epitopes to corresponding epitopes in the RV144 vaccine, the proportion of epitopes that could be matched differed depending on the protein conservation (only 36% of epitopes in Env vs 84–91% in Gag/Pol/Nef for CD8 predicted epitopes) or on vaccine insert subtype (55% against CRF01_AE vs 7% against subtype B). To compare predicted epitopes to the vaccine, we analyzed predicted binding affinity and evolutionary distance measurements. Comparisons between the vaccine and placebo arm did not reveal robust evidence for a T cell driven sieve effect, although some differences were noted in Env-V2 (0.022≤p-value≤0.231). The paucity of CD8 T cell responses identified following RV144 vaccination, with no evidence for V2 specificity, considered together both with the association of decreased infection risk in RV 144 participants with V-specific antibody responses and a V2 sieve effect, lead us to hypothesize that this sieve effect was not T cell specific. Overall, our results did not reveal a strong differential impact of vaccine-induced T cell responses among breakthrough infections in RV144 participants. Public Library of Science 2014-10-28 /pmc/articles/PMC4211711/ /pubmed/25350851 http://dx.doi.org/10.1371/journal.pone.0111334 Text en © 2014 Dommaraju et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Dommaraju, Kalpana
Kijak, Gustavo
Carlson, Jonathan M.
Larsen, Brendan B.
Tovanabutra, Sodsai
Geraghty, Dan E.
Deng, Wenjie
Maust, Brandon S.
Edlefsen, Paul T.
Sanders-Buell, Eric
Ratto-Kim, Silvia
deSouza, Mark S.
Rerks-Ngarm, Supachai
Nitayaphan, Sorachai
Pitisuttihum, Punnee
Kaewkungwal, Jaranit
O'Connell, Robert J.
Robb, Merlin L.
Michael, Nelson L.
Mullins, James I.
Kim, Jerome H.
Rolland, Morgane
CD8 and CD4 Epitope Predictions in RV144: No Strong Evidence of a T-Cell Driven Sieve Effect in HIV-1 Breakthrough Sequences from Trial Participants
title CD8 and CD4 Epitope Predictions in RV144: No Strong Evidence of a T-Cell Driven Sieve Effect in HIV-1 Breakthrough Sequences from Trial Participants
title_full CD8 and CD4 Epitope Predictions in RV144: No Strong Evidence of a T-Cell Driven Sieve Effect in HIV-1 Breakthrough Sequences from Trial Participants
title_fullStr CD8 and CD4 Epitope Predictions in RV144: No Strong Evidence of a T-Cell Driven Sieve Effect in HIV-1 Breakthrough Sequences from Trial Participants
title_full_unstemmed CD8 and CD4 Epitope Predictions in RV144: No Strong Evidence of a T-Cell Driven Sieve Effect in HIV-1 Breakthrough Sequences from Trial Participants
title_short CD8 and CD4 Epitope Predictions in RV144: No Strong Evidence of a T-Cell Driven Sieve Effect in HIV-1 Breakthrough Sequences from Trial Participants
title_sort cd8 and cd4 epitope predictions in rv144: no strong evidence of a t-cell driven sieve effect in hiv-1 breakthrough sequences from trial participants
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211711/
https://www.ncbi.nlm.nih.gov/pubmed/25350851
http://dx.doi.org/10.1371/journal.pone.0111334
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