Modification of the Association Between T-Cell Immune Responses and Human Immunodeficiency Virus Type 1 Infection Risk by Vaccine-Induced Antibody Responses in the HVTN 505 Trial

作者：Youyi Fong, Xiaoying Shen, Vicki C Ashley, Aaron Deal, Kelly E. Seaton, Chenchen Yu, Shannon Grant, Guido Ferrari, Allan C. deCamp, Robert T. Bailer, Richard A. Koup, David C. Montefiori, Barton F. Haynes, Marcella Sarzotti‐Kelsoe, Barney S. Graham, Lindsay N. Carpp, Scott M. Hammer, Magda Sobieszczyk, Shelly Karuna, Edith Swann, Edwin DeJesus, Mark J. Mulligan, Ian Frank, Susan Buchbinder, Richard M. Novak, M. Juliana McElrath, Spyros A. Kalams, Michael C. Keefer, Nicole Frahm, Holly Janes, Peter B. Gilbert, Georgia D. Tomaras · 发表于：The Journal of Infectious Diseases · 年份：2018 · DOI：10.1093/infdis/jiy008 · 被引用次数：44 · 研究领域：Virus-based gene therapy research、HIV Research and Treatment、Immunotherapy and Immune Responses

Background: HVTN 505 was a human immunodeficiency virus type 1 (HIV-1) preventive vaccine efficacy trial of a DNA/recombinant adenovirus serotype 5 (rAd5) vaccine regimen. We assessed antibody responses measured 1 month after final vaccination (month 7) as correlates of HIV-1 acquisition risk. Methods: Binding antibody responses were quantified in serum samples from 25 primary endpoint vaccine cases (diagnosed with HIV-1 infection between month 7 and month 24) and 125 randomly sampled frequency-matched vaccine controls (HIV-1 negative at month 24). We prespecified for a primary analysis tier 6 antibody response biomarkers that measure immunoglobulin G (IgG) and immunoglobulin A (IgA) binding to Env proteins and 2 previously assessed T-cell response biomarkers. Results: Envelope-specific IgG responses were significantly correlated with decreased HIV-1 risk. Moreover, the interaction of IgG responses and Env-specific CD8+ T-cell polyfunctionality score had a highly significant association with HIV-1 risk after adjustment for multiple comparisons. Conclusions: Vaccinees with higher levels of Env IgG have significantly decreased HIV-1 risk when CD8+ T-cell responses are low. Moreover, vaccinees with high CD8+ T-cell responses generally have low risk, and those with low CD8+ T-cell and low Env antibody responses have high risk. These findings suggest the critical importance of inducing a robust IgG Env response when the CD8+ T-cell response is low.