ZyCoV-D: A COVID-19 Vaccine Built on the DNA Platform

Although mRNA- and adenovirus vector-based COVID-19 vaccines have been frontrunners in the pandemic's containment, the vaccine pipeline contains additional platforms — including DNA-based vaccines such as ZyCoV-D — that have demonstrated favorable safety and immunogenicity at the phase 1/2 level. Now, investigators in India are conducting a phase 3 study in which they randomized 27,703 participants (mean age, 36.5; 7.5% aged ≥60; 67% male) 1:1 to receive three doses of ZyCoV-D or placebo. The primary outcome was occurrence of symptomatic RT-PCR–positive COVID-19 at 28 days after the last dose.

At interim analysis, the primary endpoint occurred in 20 participants in the ZyCoV-D group and 61 participants in the placebo group, for a vaccine efficacy of 66.6%. Only one case of severe COVID-19 occurred (and was in the placebo group). At day 84, seroconversion of neutralizing antibodies occurred in 88.0% of ZyCoV-D recipients and 42.5% of placebo recipients — and a 9.6-fold rise in antigen-specific interferon γ responses relative to baseline was achieved in the vaccine group, but not the placebo group. Rates of solicited and unsolicited adverse events did not differ between groups.