P17-19. Impact of single epitope-specific CD8+ T cell memory induction by prophylactic vaccination on immunodeficiency virus control

Background

Despite many efforts to develop AIDS vaccines eliciting T-cell responses, whether this approach actually results in HIV control remains unknown. It is important to determine which T-cell responses to be induced by prophylactic vaccination for HIV control after virus exposure. Virus-specific CD8+ T cells are crucial for HIV control, but the real benefit of their memory induction has not been evaluated. Here, we examined the efficacy of a prophylactic vaccine eliciting single Gag241-249 epitope-specific CD8+ T-cell responses against simian immunodeficiency virus (SIV) challenge in macaques.

Methods

We developed a prophylactic vaccine using a Sendai virus vector expressing a single, Mamu-A*90120-5-restricted Gag241-249 CTL epitope fused with EGFP protein. Eighteen Burmese rhesus macaques possessing this MHC-I allele (Mamu-A*90120-5) were divided into three groups of six animals each. Group I received no vaccination, group II a control vaccine expressing EGFP, and group III a vaccine expressing Gag241-249-EGFP fusion protein. All these three groups were challenged intravenously with SIVmac239.

Results

The vaccination resulted in induction of Gag241-249-specific CD8+ T-cell responses in group III animals. After SIV challenge, these vaccinees exhibited significantly reduced peak viral loads, followed by SIV containment at the setpoint. In the acute phase, these animals showed dominant Gag241-249-specific CD8+ T-cell responses with higher effector memory frequencies.

Conclusion

These results demonstrate that single epitope-specific memory CD8+ T cells induced by vaccination could indeed facilitate SIV control after virus exposure, indicating the rationale of a prophylactic vaccine strategy eliciting virus-specific CD8+ T-cell memory for HIV control.