Open AccessCD8 and CD4 Epitope Predictions in RV144: No Strong Evidence of a T-Cell Driven Sieve Effect in HIV-1 Breakthrough Sequences from Trial Participants
Author(s) -
Kalpana Dommaraju,
Gustavo H. Kijak,
Jonathan M. Carlson,
Brendan B. Larsen,
Sodsai Tovanabutra,
Dan Geraghty,
Wenjie Deng,
Brandon S. Maust,
Paul T. Edlefsen,
Eric SandersBuell,
Silvia RattoKim,
Mark deSouza,
Supachai Rerks-Ngarm,
Sorachai Nitayaphan,
Punnee Pitisuttihum,
Jaranit Kaewkungwal,
Robert J. O’Connell,
Merlin L. Robb,
Nelson L. Michael,
James I. Mullins,
Jerome H. Kim,
Morgane Rolland
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0111334
Subject(s) - epitope , vaccine trial , virology , hiv vaccine , placebo , vaccine efficacy , biology , cd8 , aids vaccines , immunology , antigen , vaccination , medicine , alternative medicine , pathology
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.