Analysis of HLA A*02 association with vaccine efficacy in the RV144 HIV-1 vaccine trial

Andrew J. Gartland, Sue Li, John McNevin, Georgia D. Tomaras, Raphael Gottardo, Holly Janes, Youyi Fong, Daryl Morris, Daniel E. Geraghty, Gustavo H. Kijak, Paul T. Edlefsen, Nicole Frahm, Brendan B. Larsen, Sodsai Tovanabutra, Eric Sanders-Buell, Allan C. deCamp, Craig A. Magaret, Hasan Ahmed, Jodie P. Goodridge, Lennie ChenPhilip Konopa, Snehal Nariya, Julia N. Stoddard, Kim Wong, Hong Zhao, Wenjie Deng, Brandon S. Maust, Meera Bose, Shana Howell, Adam Bates, Michelle Lazzaro, Annemarie O'Sullivan, Esther Lei, Andrea Bradfield, Grace Ibitamuno, Vatcharain Assawadarachai, Robert J. O'Connell, Mark S. deSouza, Sorachai Nitayaphan, Supachai Rerks-Ngarm, Merlin L. Robb, John Sidney, Alessandro Sette, Susan Zolla-Pazner, David Montefiori, M. Juliana McElrath, James I. Mullins, Jerome H. Kim, Peter B. Gilbert, Tomer Hertz

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Abstract

The RV144 HIV-1 vaccine trial demonstrated partial efficacy of 31% against HIV-1 infection. Studies into possible correlates of protection found that antibodies specific to the V1 and V2 (V1/V2) region of envelope correlated inversely with infection risk and that viruses isolated from trial participants contained genetic signatures of vaccine-induced pressure in the V1/V2 region.We explored the hypothesis that the genetic signatures in V1 and V2 could be partly attributed to selection by vaccine-primed T cells.We performed a T-cell based sieve analysis of breakthrough viruses in the RV144 trial and found evidence of predicted HLA binding escape that was greater in vaccine versus placebo recipients. The predicted escape depended on class I HLA A*02- and A*11-restricted epitopes in the MN strain rgp 120 vaccine immunogen. Though we hypothesized that this was indicative of postacquisition selection pressure, we also found that vaccine efficacy (VE) was greater in A*02-positive (A*02+) participants than in A*02- participants (VE = 54% versus 3%, P = 0.05). Vaccine efficacy against viruses with a lysine residue at site 169, important to antibody binding and implicated in vaccine-induced immune pressure, was also greater in A*02+ participants (VE = 74% versus 15%, P = 0.02). Additionally, a reanalysis of vaccine-induced immune responses that focused on those that were shown to correlate with infection risk suggested that the humoral responses may have differed in A*02+ participants. These exploratory and hypothesis-generating analyses indicate there may be an association between a class I HLA allele and vaccine efficacy, highlighting the importance of considering HLA alleles and host immune genetics in HIV vaccine trials.

Original languageEnglish
Pages (from-to)8242-8255
Number of pages14
JournalJournal of Virology
Volume88
Issue number15
DOIs
StatePublished - 1 Jan 2014

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