HIV-1 Vaccine-Induced T-Cell Reponses Cluster in Epitope Hotspots that Differ from Those Induced in Natural Infection with HIV-1

PLoS Pathogens

Susan Buchbinder¹  Danilo R. Casimiro²  Michael N. Robertson²  David P. Friedrich³  M. Juliana McElrath³  Nicole Frahm³  Lawrence Corey³  Hasan Ahmed³  Steven G. Self³  Peter Gilbert³  Tomer Hertz³  Barney S. Graham⁴  Helen Horton⁵ 

[1] HIV Research Section, San Francisco Department of Public Health, San Francisco, California, United States of America;Merck Research Laboratories, West Point, Pennsylvania, United States of America;Statistical Center for HIV Research and Prevention, Vaccine and Infectious Disease Division and the HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America;Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America;Viral Vaccine Program, Seattle Biomedical Research Institute, Seattle, Washington, United States of America

关键词: Epitope mapping;    Vaccines;    HIV vaccines;    HIV-1;    HIV;    Immune response;    T cells;    Forecasting;   

DOI  :  10.1371/journal.ppat.1003404

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Several recent large clinical trials evaluated HIV vaccine candidates that were based on recombinant adenovirus serotype 5 (rAd-5) vectors expressing HIV-derived antigens. These vaccines primarily elicited T-cell responses, which are known to be critical for controlling HIV infection. In the current study, we present a meta-analysis of epitope mapping data from 177 participants in three clinical trials that tested two different HIV vaccines: MRKAd-5 HIV and VRC-HIVAD014-00VP. We characterized the population-level epitope responses in these trials by generating population-based epitope maps, and also designed such maps using a large cohort of 372 naturally infected individuals. We used these maps to address several questions: (1) Are vaccine-induced responses randomly distributed across vaccine inserts, or do they cluster into immunodominant epitope hotspots? (2) Are the immunodominance patterns observed for these two vaccines in three vaccine trials different from one another? (3) Do vaccine-induced hotspots overlap with epitope hotspots induced by chronic natural infection with HIV-1? (4) Do immunodominant hotspots target evolutionarily conserved regions of the HIV genome? (5) Can epitope prediction methods be used to identify these hotspots? We found that vaccine responses clustered into epitope hotspots in all three vaccine trials and some of these hotspots were not observed in chronic natural infection. We also found significant differences between the immunodominance patterns generated in each trial, even comparing two trials that tested the same vaccine in different populations. Some of the vaccine-induced immunodominant hotspots were located in highly variable regions of the HIV genome, and this was more evident for the MRKAd-5 HIV vaccine. Finally, we found that epitope prediction methods can partially predict the location of vaccine-induced epitope hotspots. Our findings have implications for vaccine design and suggest a framework by which different vaccine candidates can be compared in early phases of evaluation.

【 授权许可】

CC BY