Toxicity and Local Tolerance of COVID- e Vax, a Plasmid DNA Vaccine for SARS-CoV-2, Delivered by Electroporation

Toxicol Pathol. 2021 Oct;49(7):1255-1268. doi: 10.1177/01926233211042263. Epub 2021 Sep 8.


COVID-19 is a rapidly spreading disease, posing a huge hazard to global health. The plasmid vaccine pTK1A-TPA-SpikeA (named COVID-eVax) encodes the severe acute respiratory syndrome coronavirus 2 S protein receptor-binding domain, developed for intramuscular injection followed by electroporation (EP). The aim of this study was to assess the systemic toxicity and local tolerance of COVID-eVax delivered intramuscularly followed by EP in Sprague Dawley (SD) rats. The animals were killed 2 days and 4 weeks after the last injection (30-day and 57-day, respectively). No mortality was observed, and no signs of toxicity were evident, including injection site reactions. A lasting and specific immune response was observed in all treated animals, confirming the relevance of the rat as a toxicological model for this vaccine. Histopathological evaluation revealed muscle fiber necrosis associated with subchronic inflammation at the injection sites (at the 30-day time point), with a clear trend for recovery at the 57-day time point, which is expected following EP, and considered a desirable effect to mount the immune response against the target antigen. In conclusion, the intramuscular EP-assisted DNA vaccine, COVID-eVax showed an excellent safety profile in SD rats under these experimental conditions and supports its further development for use in humans.

Keywords: COVID-19; SD rats; electroporation; safety; toxicity; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral
  • COVID-19 Vaccines
  • COVID-19*
  • Electroporation
  • Humans
  • Plasmids
  • Rats
  • Rats, Sprague-Dawley
  • SARS-CoV-2
  • Vaccines, DNA* / toxicity


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