SARS-CoV-2 DNA Vaccine INO-4800 Induces Durable Immune Responses Capable of Being Boosted in a Phase 1 Open-Label Trial
Kimberly A. Kraynyak, Elliott Blackwood, Joseph Agnes, Pablo Tebas, Mary Giffear, Dinah Amante, Emma L. Reuschel, Mansi Purwar, Aaron Christensen-Quick, Neiman Liu, Viviane M. Andrade, Malissa Diehl, Snehal Wani, M. Łupicka, Albert J. Sylvester, Matthew P. Morrow, Patrick Pezzoli, Trevor McMullan, Abhijeet J. Kulkarni, Faraz I. Zaidi, Drew Frase, Kevin Liaw, Trevor R.F. Smith, Stephanie Ramos, John Ervin, Mark E. Adams, Jessica Lee, Michael Dallas, Ami Shah Brown, Jacqueline E. Shea, J Joseph Kim, David B. Weiner, Kate E. Broderick, Laurent Humeau, Jean Boyer, Mammen P. Mammen
Abstract
BACKGROUND: Additional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines that are safe and effective as primary vaccines and boosters remain urgently needed to combat the coronavirus disease 2019 (COVID-19) pandemic. We describe safety and durability of immune responses following 2 primary doses and a homologous booster dose of an investigational DNA vaccine (INO-4800) targeting full-length spike antigen. METHODS: Three dosage strengths of INO-4800 (0.5 mg, 1.0 mg, and 2.0 mg) were evaluated in 120 age-stratified healthy adults. Intradermal injection of INO-4800 followed by electroporation at 0 and 4 weeks preceded an optional booster 6-10.5 months after the second dose. RESULTS: INO-4800 appeared well tolerated with no treatment-related serious adverse events. Most adverse events were mild 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 significantly increased in the 2.0-mg dose group. CONCLUSIONS: INO-4800 was well tolerated in a 2-dose primary series and homologous booster in all adults, including elderly participants. These results support further development of INO-4800 for use as primary vaccine and booster. CLINICAL TRIALS REGISTRATION: NCT04336410.