A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19

The COVID-19 pandemic and the need for additional safe, effective, and affordable vaccines gave new impetus into development of vaccine genetic platforms. Here we report the findings from the phase 1, first-in-human, dose-escalation study of COVID-eVax, a DNA vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Sixty-eight healthy adults received two doses of 0.5, 1, or 2 mg 28 days apart, or a single 2-mg dose, via intramus-cular injection followed by electroporation, and they were monitored for 6 months. All participants completed the pri-mary safety and immunogenicity assessments after 8 weeks. COVID-eVax was well tolerated, with mainly mild to moder-ate solicited adverse events (tenderness, pain, bruising, head-ache, and malaise/fatigue), less frequent after the second dose, and it induced an immune response (binding antibodies and/or T cells) at all prime-boost doses tested in up to 90% of the volunteers at the highest dose. However, the vaccine did not induce neutralizing antibodies, while particularly relevant was the T cell-mediated immunity, with a robust Th1 response. This T cell-skewed immunological response adds significant information to the DNA vaccine platform and should be assessed in further studies for its protective ca-pacity and potential usefulness also in other therapeutic areas, such as oncology.