The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection

Background: Therapeutic vaccination is being studied in eradication and "functional cure" strategies for HIV-1. The Profectus Biosciences multiantigen (MAG) HIV-1 DNA vaccine encodes HIV-1 Gag/Pol, Nef/Tat/Vif, and Envelope, and interleukin-12 (IL-12) and is delivered by electroporation combined with intramuscular injection (IM-EP). Methods: Sixty-two HIV-1-infected patients on antiretroviral therapy (plasma HIV-1 RNA levels ≤200 copies/mL; CD4 + T-cell counts ≥500 cells/mm 3) were randomly allocated 5:1 to receive vaccine or placebo. At weeks 0, 4, and 12, 4 consecutive cohorts received 3000 g HIV MAG pDNA with 0, 50, 250, or 1000 g of IL-12 pDNA by IM-EP. A fifth cohort received HIV MAG pDNA and 1000 g of IL-12 pDNA by standard IM injection. Results: CD4 + T cells expressing IL-2 in response to Gag and Pol and interferon-γ responses to Gag, Pol, and Env increased from baseline to week 14 in the low-dose (50-g) IL-12 arm vs. placebo (P < 0.05; intracellular cytokine staining). The total increase in the IL-2-expressing CD4 + T-cell responses to any antigen was also higher in the low-dose IL-12 arm vs. placebo (P 0.04). Cytokine responses by CD8 T cells to HIV antigens were not increased in any vaccine arm relative to placebo. Conclusions: HIV-1 MAG/low-dose IL-12 DNA vaccine delivered by IM-EP augmented CD4 + but not CD8 + T-cell responses to multiple HIV-1 antigens.