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

J Infect Dis. 2022 Jun 1;225(11):1923-1932. doi: 10.1093/infdis/jiac016.


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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral
  • Antibody Formation
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Humans
  • Immunogenicity, Vaccine
  • SARS-CoV-2
  • Vaccination / adverse effects
  • Vaccines, DNA* / adverse effects


  • Antibodies, Viral
  • COVID-19 Vaccines
  • Vaccines, DNA
  • reluscovtogene ralaplasmid

Associated data