DNA Priming Increases Frequency of T-Cell Responses to a Vesicular Stomatitis Virus HIV Vaccine with Specific Enhancement of CD8+ T-Cell Responses by Interleukin-12 Plasmid DNA.

HVTN 087 assessed the effect of increasing doses of pIL-12 adjuvant on the immunogenicity of a HIV-1 multi-antigen (MAG) DNA vaccine delivered by electroporation and boosted with an attenuated VSV-Gag vaccine. We randomized 100 healthy adults to receive placebo, or 3mg HIV-MAG ( gag/pol, env, nef/tat/vif ) DNA vaccine co-administered with pIL-12 at 0μg, 250μg, 1,000μg or 1,500μg intramuscularly by electroporation at 0, 1 and 3 months followed by intramuscular inoculation with 3.4×10 7 PFU VSV-Gag vaccine at 6 months. Immune responses were assessed after prime, boost and 6 months after the last vaccination. High dose pIL-12 increased the magnitude of CD8 + T cell responses post boost compared to no pIL-12 ( P =0.02), while CD4 + T-cell responses after the prime were higher in the absence of pIL-12 compared to low and medium dose pIL-12 ( P ≤0.05). The VSV boost increased Gag-specific CD4 + and CD8 + T-cell responses in all groups ( P + T cells), inducing a median of four Gag epitopes in responders. Six to nine months after the boost, responses decreased in magnitude, but CD8 + T-cell response rates were maintained. The addition of a DNA prime dramatically improved responses to the VSV vaccine tested previously in HVTN 090, leading to broad epitope targeting and maintained CD8 + T-cell response rates at early memory. The addition of a high dose pIL-12 given with a DNA prime by electroporation and boosted with VSV-Gag increased CD8 + but decreased CD4 + T-cell responses. This approach may be advantageous in reshaping the T-cell responses to a variety of chronic infections or tumors.