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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
Authors: Kalpana Dommaraju
Gustavo Kijak
Jonathan M. Carlson
Brendan B. Larsen
Sodsai Tovanabutra
Dan E. Geraghty
Wenjie Deng
Brandon S. Maust
Paul T. Edlefsen
Eric Sanders-Buell
Silvia Ratto-Kim
Mark S. 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
Walter Reed Army Institute of Research
Henry Jackson Foundation
Microsoft Research
University of Washington, Seattle
Fred Hutchinson Cancer Research Center
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Mahidol University
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 28-Oct-2014
Citation: PLoS ONE. Vol.9, No.10 (2014)
Abstract: © 2014 Dommaraju et al. 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.
ISSN: 19326203
Appears in Collections:Scopus 2011-2015

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