Rabies virus-based vaccines elicit neutralizing antibodies, poly-functional CD8 + T cell, and protect rhesus macaques from AIDS-like disease after SIV mac251 challenge

Abstract

Highly attenuated rabies virus (RV) vaccine vectors were evaluated for their ability to protect against highly pathogenic SIV mac251 challenge. Mamu-A*01 negative rhesus macaques were immunized in groups of four with either: RV expressing SIV mac239-GagPol, a combination of RV expressing SIV mac239-Env and RV expressing SIV mac239-GagPol, or with empty RV vectors. Eight weeks later animals received a booster immunization with a heterologous RV expressing the same antigens. At 12 weeks post-boost, all animals were challenged intravenously with 100 TCID 50 of pathogenic SIV mac251-CX. Immunized macaques in both vaccine groups had 1.3–1.6-log-fold decrease in viral set point compared to control animals. The GagPol/Env immunized animals also had a significantly lower peak viral load. When compared to control animals following challenge, vaccinated macaques had a more rapid induction of SIV mac251 neutralizing antibodies and of CD8 + T cell responses to various SIV epitopes. Moreover, vaccinated macaques better maintained peripheral memory CD4 + T cells and were able to mount a poly-functional CD8 + T cell response in the mucosa. These findings indicate promise for RV-based vectors and have important implications for the development of an efficacious HIV vaccine.