A novel vaccine regimen utilizing DNA, vaccinia virus and protein immunizations for HIV-1 envelope presentation

Recombinant DNA and vaccinia virus (VV) vectors that express envelope (Env) proteins of the human immunodeficiency virus (HIV) have each been prominently utilized in vaccine development. These two vectors (termed DNA-Env and VV-Env) are attractive vaccine candidates due to their abilities to elicit both cytotoxic T-lymphocyte and B-cell responses. Our previous work demonstrated that DNA-Env primed animals, that were relatively unresponsive to DNA-Env boosters, could be immunized with VV-Env to yield more than a 100-fold increase in antibody responses. Here we show: (1) results with an optimized vaccine regimen that primes with DNA-Env, boosts with VV-Env, and re-boosts with purified Env proteins, (2) enhanced responses with 8 rather than 16 week intervals between VV-Env and protein immunizations, and (3) the failure of single Env vaccines to reproducibly elicit responses toward heterologous Env, regardless of the vaccination regimen utilized. Results encourage the use of poly-Env vaccine cocktails administered via DNA/VV/protein regimens in future non-human primate and clinical studies.