We developed a candidate DNA vaccine called “DNA-4”consisting of 4 plasmid DNAs encoding Nef, Gag, Pol(rt), and gp140 HIV-1 proteins. The vaccine was found to be safe and immunogenic in a phase I clinical trial. Here we present the results of a phase II clinical trial of “DNA-4”. This was a multicenter, double-blind, placebo-controlled clinical trial of safety, and dose selection of “DNA-4” in HIV-1 infected people receiving antiretroviral therapy (ART). Fifty-four patients were randomized into 3 groups (17 patients—group DNA-4 0.25 mg, 17 patients—group DNA-4 0.5 mg, 20 patients—the placebo group). All patients were immunized 4 times on days 0, 7, 11, and 15 followed by a 24-week follow-up period. “DNA-4” was found to be safe and well-tolerated at doses of 0.25 mg and 0.5 mg. We found that the amplitudes of the spontaneous viral load increases in three patients immunized with the candidate DNA vaccine were much higher than that in placebo group—2800, 180,000 and 709 copies/mL, suggesting a possible influence of therapeutic DNA vaccination on viral reservoirs in some patients on ART. We hypothesize that this influence was associated with the reactivation of proviral genomes.
Simple, scalable and robust purification of two HIV-1 subtype C gp120 monomer subunit antigens for phase II clinical trial in Republic of South Africa
