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 C Diehl, Snehal Wani, Martyna Lupicka, Albert Sylvester, Matthew P Morrow, Patrick Pezzoli, Trevor McMullan, Abhijeet J Kulkarni, Faraz I Zaidi, Drew Frase, Kevin Liaw, Trevor R F Smith, Stephanie J Ramos, John Ervin, Mark Adams, Jessica Lee, Michael Dallas, Ami Shah Brown, Jacqueline E Shea, J Joseph Kim, David B Weiner, Kate E Broderick, Laurent M Humeau, Jean D Boyer, Mammen P Mammen, 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 C Diehl, Snehal Wani, Martyna Lupicka, Albert Sylvester, Matthew P Morrow, Patrick Pezzoli, Trevor McMullan, Abhijeet J Kulkarni, Faraz I Zaidi, Drew Frase, Kevin Liaw, Trevor R F Smith, Stephanie J Ramos, John Ervin, Mark Adams, Jessica Lee, Michael Dallas, Ami Shah Brown, Jacqueline E Shea, J Joseph Kim, David B Weiner, Kate E Broderick, Laurent M Humeau, Jean D 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.
Keywords: COVID-19; DNA vaccine; INO-4800; SARS-CoV-2; booster; clinical trial; immunogenicity; safety.
© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Source: PubMed