SARS-CoV-2 DNA Vaccine INO-4800 Induces Durable Immune Responses Capable of Being Boosted in a Phase 1 Open-Label Trial

Kraynyak, K. A.; Blackwood, E.; Agnes, J.; Tebas, P.; Giffear, M.; Amante, D.; Reuschel, E. L.; Purwar, M.; Christensen-Quick, A.; Liu, N.; Andrade, V.; Diehl, M.; Wani, S.; Lupicka, M.; Sylvester, A.; Morrow, M. P.; Pezzoli, P.; McMullan, T.; Kulkarni, A. J.; Zaidi, F. I.; Frase, D.; Liaw, K.; Smith, T. R. F.; Ramos, S. J.; Ervin, J.; Adams, M.; Lee, J.; Dallas, M.; Shah Brown, A.; Shea, J. E.; Kim, J. J.; Weiner, D. B.; Broderick, K. E.; Humeau, L. M.; Boyer, J. D.; Mammen, M. P.

Background: Additional SARS-CoV-2 vaccines that are safe and effective as both primary series and booster remain urgently needed to combat the COVID-19 pandemic. Here we describe the safety and durability of the immune response from two doses of a DNA vaccine (INO-4800) targeting the full-length Spike antigen and a subsequent homologous booster dose. Methods: INO-4800 was evaluated in 120 healthy participants across three dose groups (0.5 mg, 1.0 mg and 2.0 mg), each stratified by age. INO-4800 was injected intradermally followed by electroporation at 0 and 4 weeks followed by an optional booster dose 6-10.5 months following the second dose. Results: INO-4800 was well-tolerated, with no treatment-related serious adverse events reported. Most adverse events were mild in severity and did not increase in frequency with age and subsequent dosing. A durable antibody response was observed 6 months following the second dose; a homologous booster dose significantly increased immune responses. Cytokine producing T cells and activated CD8+T cells with lytic potential were detected in the 2.0 mg dose group. Conclusion: INO-4800 was well-tolerated as a 2-dose series and as a homologous booster dose in all adults, including the elderly. These results support further development of INO-4800 as a primary series and as a booster. Keywords: SARS-CoV-2; Clinical trial; DNA Vaccine; COVID-19; Immunogenicity; Booster