Live attenuated rubella vectors express HIV Env and SIV Gag antigens in the context of an acute infection and elicit high antibody titers, memory B cells, and Gag specific CD8+ T cells (VIR5P.1033)

Abstract

Abstract Live attenuated viral strains are among our most potent vaccines. We have used the live attenuated rubella vaccine strain RA27/3 as a vector to express HIV MPER and SIV Gag antigens. These vectors combine the potency, durability and safety of rubella vaccine with the antigenicity of the inserts. We have recently completed the first successful trial of live rubella vectors in rhesus macaques. Rubella vectors grew robustly in macaques, and the vaccine inserts were strongly immunogenic. Simultaneous immunization with two vectors elicited antibodies to both inserts. Anti-Gag antibodies after immunization reached titers equal to natural SIV infection. Antibodies persisted for at least one year and declined at the same rate as anti-rubella antibodies, which protect for life. Re-exposure to the vector boosted the immune response, indicating the induction of memory B cells. Priming with DNA vaccine and boosting with the vector produced high levels of Gag specific CD8+ T cells. The vector can stably express larger inserts, up to 320 amino acids for SIV Gag proteins, including part of MA and all of CA and P2 proteins. They also express engineered HIV Env outer domains up to 180 amino acids that include the CD4 binding site and bind monoclonal VRC01. Rhesus macaques will provide the ideal animal model for evaluating novel vaccine inserts for immunogenicity, induction of neutralizing antibodies, and protection against SIV or SHIV challenge.