期刊
JOURNAL OF INFECTIOUS DISEASES
卷 215, 期 9, 页码 1376-1385出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jix086
关键词
correlates of risk; HIV-1 vaccine; HVTN 505 vaccine efficacy trial; intracellular cytokine staining; machine learning analyses; T-cell immunogenicity; T-cell polyfunctionality; vaccine-induced immune response
资金
- National Institute of Allergy and Infectious Disease at the National Institutes of Health [UM1 AI068618, UM1 AI068635, UM1 AI068614, UM1 AI069470]
Background. It is important to identify vaccine-induced immune responses that predict the preventative efficacy of a human immunodeficiency virus (HIV)-1 vaccine. We assessed T-cell response markers as correlates of risk in the HIV Vaccine Trials Network (HVTN) 505 HIV-1 vaccine efficacy trial. Methods. 2504 participants were randomized to DNA/rAd5 vaccine or placebo, administered at weeks 0, 4, 8, and 24. Peripheral blood mononuclear cells were obtained at week 26 from all 25 primary endpoint vaccine cases and 125 matched vaccine controls, and stimulated with vaccine-insert-matched peptides. Primary variables were total HIV-1-specific CD4(+) T-cell magnitude and Env-specific CD4+ polyfunctionality. Four secondary variables were also assessed. Immune responses were evaluated as predictors of HIV-1 infection among vaccinees using Cox proportional hazards models. Machine learning analyses identified immune response combinations best predicting HIV-1 infection. Results. We observed an unexpectedly strong inverse correlation between Env-specific CD8(+) immune response magnitude and HIV-1 infection risk (hazard ratio [HR] = 0.18 per SD increment; P =.04) and between Env-specific CD8+ polyfunctionality and infection risk (HR = 0.34 per SD increment; P < .01). Conclusions. Further research is needed to determine if these immune responses are predictors of vaccine efficacy or markers of natural resistance to HIV-1 infection.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据