Impact of Vaccination on Cytotoxic T Lymphocyte Immunodominance and Cooperation against Simian Immunodeficiency Virus Replication in Rhesus Macaques

摘要

Cytotoxic T lymphocyte (CTL) responses play a central role in viral suppression in human immunodeficiency virus (HIV) infections. Prophylactic vaccination resulting in effective CTL responses after viral exposure would contribute to HIV control. It is important to know how CTL memory induction by vaccination affects postexposure CTL responses. We previously showed vaccine-based control of a simian immunodeficiency virus (SIV) challenge in a group of Burmese rhesus macaques sharing a major histocompatibility complex class I haplotype. Gag206-216 and Gag241-249 epitope-specific CTL responses were responsible for this control. In the present study, we show the impact of individual epitope-specific CTL induction by prophylactic vaccination on postexposure CTL responses. In the acute phase after SIV challenge, dominant Gag206-216-specific CTL responses with delayed, naive-derived Gag241-249-specific CTL induction were observed in Gag206-216 epitope-vaccinated animals with prophylactic induction of single Gag206-216 epitope-specific CTL memory, and vice versa in Gag241-249 epitope-vaccinated animals with single Gag241-249 epitope-specific CTL induction. Animals with Gag206-216-specific CTL induction by vaccination selected for a Gag206-216-specific CTL escape mutation by week 5 and showed significantly less decline of plasma viral loads from week 3 to week 5 than in Gag241-249 epitope-vaccinated animals without escape mutations. Our results present evidence indicating significant influence of prophylactic vaccination on postexposure CTL immunodominance and cooperation of vaccine antigen-specific and non-vaccine antigen-specific CTL responses, which affects virus control. These findings provide great insights into antigen design for CTL-inducing AIDS vaccines.