Analysis of HLA A*02 Association with Vaccine Efficacy in the RV144 HIV-1 Vaccine Trial

作者：Andrew J. Gartland, Sue Li, John McNevin, Georgia D. Tomaras, Raphaël Gottardo, Holly Janes, Youyi Fong, Daryl E. 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 Chen, Philip Konopa, Snehal Nariya, Julia N. Stoddard, Kim Wong, Hong Zhao, Wenjie Deng, Brandon S. Maust, Meera Bose, Shana Howell, Adam Bates, Michelle Lazzaro, Anne Marie 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 C. Montefiori, M. Juliana McElrath, James I. Mullins, Jérôme H. Kim, Peter B. Gilbert, Tomer Hertz · 发表于：Journal of Virology · 年份：2014 · DOI：10.1128/jvi.01164-14 · 被引用次数：65 · 研究领域：HIV Research and Treatment、vaccines and immunoinformatics approaches、T-cell and B-cell Immunology

UNLABELLED: 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 rgp120 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...