We compared immunogenicity and protective efficacy of an HIV vaccine comprised of DNA (env and gag) and Env proteins by co-administration of DNA and Protein in the same muscle or by separate administration of the DNA and Protein components in contralateral sites.
Female rhesus macaques (20 animals/group) were immunized with a 6-valent vaccine including DNA plasmids expressing membrane-anchored gp145 Env sequentially isolated from a HIV-1 infected individual (CH505). The DNA was delivered by IM injection followed by in vivo electroporation. The vaccine also included a gp120 Env protein component matching the sequences encoded by the plasmid DNA and adjuvanted in GLA-SE. The DNA and protein vaccine components were administered in the same anatomical sites (‘Co-administration’) or in contralateral sites (‘Separate Administration’) After 6 vaccinations in 4-month intervals, the macaques were challenged by weekly intravaginal exposures with low dose T/F tier-2 SHIV CH505 stock.
Only macaques in the co-administration vaccine group were protected against SHIV CH505 acquisition, with a 67% risk reduction per exposure after 15 weekly IVAG challenges. Macaques in the co-administration group developed higher Env-specific humoral and cellular immune responses. Non-neutralizing Env antibodies, ADCC and antibodies binding to Fc-gamma Receptor IIIa were associated with decreased transmission risk. These data suggest that simultaneous recognition, processing and presentation of DNA + Env protein in the same draining lymph node play a critical role in the development of protective immunity.
Co-immunization of DNA+Protein in the same muscle is superior for inducing protective immune responses against repeated tier-2 SHIV challenge. The advantage of co-immunization vaccine regimens targeting immunogens to the same draining LN could also be beneficial to other vaccine modalities and other pathogens.