Co-immunization of DNA and Protein in the Same Anatomical Sites Induces Superior Protective Immune Responses against SHIV Challenge

We compare immunogenicity and protective efficacy of an HIV vaccine comprised of env and gag DNA and Env (Envelope) proteins by co-administration of the vaccine components in the same muscles or by separate administration of DNA + protein in contralateral sites in female rhesus macaques. The 6-valent vaccine includes gp145 Env DNAs, representing six sequentially isolated Envs from the HIV-infected individual CH505, and matching GLA-SE-adjuvanted gp120 Env proteins. Interestingly, only macaques in the co-administration vaccine group are protected against SHIV CH505 acquisition after repeated low-dose intravaginal challenge and show 67% risk reduction per exposure. Macaques in the co-administration group develop higher Env-specific humoral and cellular immune responses. Non-neutralizing Env antibodies, ADCC, and antibodies binding to FcγRIIIa are associated with decreased transmission risk. These data suggest that simultaneous recognition, processing, and presentation of DNA + Env protein in the same draining lymph nodes play a critical role in the development of protective immunity. [Display omitted] •DNA + protein vaccine includes six sequentially isolated patient CH505 HIV Envs•DNA + Env protein co-administration in the same muscle reduces SHIV infection risk•Protection from infection is mediated by non-neutralizing antibody functions•Antibody binding to FcγRIIIa and ADCC activity contributes to protection Felber et al. show that immune responses induced by an HIV DNA and protein combination vaccine co-administered simultaneously in the same anatomical site reduce infection risk upon pathogenic SHIV challenge, compared to separate delivery of the same DNA and protein components in contralateral sites.