The goal of this project is to define the molecular and cellular mechanisms by which IL-15 programs protective immunity with the RhCMV-SIV vaccine to inform our understanding of HCMV-HIV vaccine immunity against HIV.
The world is in need of an effective HIV/AIDS vaccine, and the cytomegalovirus (CMV) vector-based HIV/SIV vaccine featured in our studies is highly efficacious and durable to uniquely mediate viral “replication arrest” efficacy in the Rhesus Macaque-SIV model. Vaccine immunity is mediated by unconventional MHC-E-restricted CD8+ T cell responses and induction of IL-15, which correlate with vaccine protection. The work proposed in this application will reveal the molecular mechanisms of immune programming by the CMV-based vaccine and IL- 15 actions to inform human testing of this vaccine concept in ongoing and future phase I/II trials.