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

Abstract

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 μg HIV MAG pDNA with 0, 50, 250, or 1000 μg of IL-12 pDNA by IM-EP. A fifth cohort received HIV MAG pDNA and 1000 μg 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-μg) 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.

Trial registration: ClinicalTrials.gov NCT01266616.

Figure 1

Baseline and week 14 percentage of CD4⁺ T cells expressing interleukin-2 (IL-2) in response to Gag2 and Pol1. Each line represents a participant’s percentage of CD4⁺ T cells responding to a specific antigen over time. IM/EP, electroporation after intramuscular injection.

Figure 2

Changes in percentage of CD4⁺ cells generating cytokines in response to selected antigens. One outlier value (+0.7%) in the placebo arm for CD4⁺ cells generating interferon-γ (IFNg)-positive responses in response to Gag2 is not plotted. The increase in response from baseline to week 14 for the low-dose (50-μg) interleukin-12 (IL-12) arm was significantly higher compared with the placebo arm for (a) IL-2⁺ response to (i) Gag2 (median = 0.01% vs. −0.01% [124 vs. −69 per 10⁶ CD4⁺ cells], P = 0.001); (ii) Pol1 (0.02% vs. 0.01% [216 vs. 102 per 10⁶ CD4⁺ cells] P = 0.022); and for (b) IFN-γ-positive response to (i) Gag2 (0.01% vs. −0.003% [120 vs. −29 per 10⁶ CD4⁺ cells], P = 0.019); and (iii) Pol1 (0.02% vs. −0.001% [244 vs. −5 per 10⁶ CD4⁺ cells], P = 0.008). IM/EP, electroporation after intramuscular injection.

Figure 3

Changes in percentage of CD8⁺ cells generating cytokines/markers in response to selected antigens. One outlier value (+2.9%) in the placebo arm for CD8⁺ cells generating interferon-γ (IFNg)-positive responses to Gag1 is not plotted. IL, interleukin; IM/EP, electroporation after intramuscular injection.