Rubella/SIV vectors for immunotherapy of SIV infection in rhesus macaques

Abstract Currently available anti-retroviral therapy (ART) can fully suppress viremia after SIV infection in macaques, but the drugs do not cure infection. When ART drugs are withdrawn, the virus rebounds vigorously. Apparently, ART cannot control or eliminate viral reservoirs. We postulate that early ART, combined with induction of strong T-cell immunity via live viral vectors, can achieve a functional cure by reducing or eliminating long-lived viral reservoirs. This could be detected as lack of viral rebound when ART is stopped. We have developed the rubella vaccine strain (RA27/3)as a live attenuated viral vector that was safe and highly immunogenic in rhesus macaques. Rubella vectors-expressing SIV Gag replicated vigorously in vivo while eliciting potent T cellimmunity to gag. The vectors alsoelicited anti-Gag antibodies that were equal to SIV infection, durable for >1 year, and were boosted by re-exposure to the vector. We are testing immunotherapy in a three stage experiment: 1st stage, SIV infection followed by starting ART on day 3; 2nd, Immunizing with SIV/Gag vectors while on ART; 3rd Stopping ART and measuring viral rebound. So far, we have shown complete viral suppression while on ART and a good immune response to the rubella vector and to the gag insert. Pending viral loads will indicate whether all control animals were infected by SIV, and any reduction or delay in viral rebound due to immunotherapy effects on the viral reservoir. The results in primate models may predict the effect of immune therapy on recent HIV infection of humans. This approach could be ideal for treating HIV infection in infants, since the viral reservoir is small, and the immune system is still intact and capable of responding to the rubella/gagvector.