A plasmid DNA vaccine against SARS-CoV-2 has been found to induce immunity in animal trials. Few other DNA based vaccine candidates are at early stages of clinical trials. Interestingly, plasmid DNA vaccines can be developed in a short period of time. Compared to attenuated and inactivated vaccines, it has several advantages. But, unlike mRNA vaccines, DNA vaccines may possibly replicate in the cell.
According to a research report published on a preprint server, the pVAX1-SARS-CoV2-co, a plasmid DNA vaccine candidate against SARS-CoV-2 has been found to induce potent immune response in animal model when delivered intradermally via pyro-drive jet injector (PJI) (1). This vaccine candidate may proceed into clinical trials soon.
Earlier, the preclinical development of DNA-based COVID-19 vaccine, INO-4800 using plasmid pGX9501 has been reported (2). This vaccine candidate is currently undergoing clinical trial (3). Few other DNA based COVID-19 vaccines are at early stages of clinical trials. For example, recruitment is in progress for NCT04673149, NCT04334980 and NCT04447781 while the trials NCT04627675 and NCT04591184 are not yet recruiting (4).
The idea to use genetically engineered plasmid DNA in vaccine form to elicit immune response has been in vogue for more than two decades. Its biology is well understood now. The results from several preclinical studies have been encouraging. Also, four DNA vaccines have been licenced recently for veterinary use (5). Efforts have been made for regulatory convergence across the world and to promote guidelines for trials of DNA vaccines to assess its safety and efficacy (6).
In view of extraordinary situation presented by the pandemic and because plasmid DNA vaccines can be developed in a short period of time, there have been spurt of activities in the area of DNA vaccine development.
DNA based vaccines offers several advantages. Unlike attenuated or inactivated vaccines, non-live vaccines based on plasmid DNA or mRNA do not have safety issues associated with live vaccines like reversion risks, unintentional spread or production errors. DNA vaccines induce antibody production (humoral immunity). It also induces killer cytotoxic T lymphocytes offering cellular immunity (5).
Compared to mRNA vaccines which are unstable and need storage at very low temperatures, DNA vaccines have an advantage as DNA is relatively stable and can be stored and distributed at 2-8 degree centigrade. But unlike mRNA vaccines which cannot replicate in the cells (7), DNA vaccines can theoretically replicate and incorporate with the genome. Long term implications of this possibility will not be easy to know in short span of clinical trials.
- Nishikawa T., Chang C.Y., et al 2021. Anti-CoVid19 plasmid DNA vaccine induces a potent immune response in rodents by Pyro-drive Jet Injector intradermal inoculation. Posted January 14, 2021. Preprint bioRxiv. DOI: https://doi.org/10.1101/2021.01.13.426436
- Smith, T.R.F., Patel, A., Ramos, S. et al. Immunogenicity of a DNA vaccine candidate for COVID-19. Published: 20 May 202. Nat Commun 11, 2601 (2020). DOI: https://doi.org/10.1038/s41467-020-16505-0
- ClinicalTrial.gov 2021. Safety, Immunogenicity, and Efficacy of INO-4800 for COVID-19 in Healthy Seronegative Adults at High Risk of SARS-CoV-2 Exposure. Identifier: NCT04642638. Available online at https://clinicaltrials.gov/ct2/show/NCT04642638?term=INO-4800&cond=Covid19&draw=2&rank=1 Accessed on 15 January 2021.
- ClinicalTrial.gov 2021. Search – plasmid DNA vaccine | Covid19. Available online at https://clinicaltrials.gov/ct2/results?cond=Covid19&term=plasmid+DNA+vaccine&cntry=&state=&city=&dist= Accessed on 15 January 2021.
- Kutzler, M., Weiner, D. DNA vaccines: ready for prime time?. Nat Rev Genet 9, 776–788 (2008). DOI: https://doi.org/10.1038/nrg2432
- Sheets, R., Kang, HN., Meyer, H. et al. WHO informal consultation on the guidelines for evaluation of the quality, safety, and efficacy of DNA vaccines, Geneva, Switzerland, December 2019. Meeting Report. Published: 18 June 2020. npj Vaccines 5, 52 (2020). DOI: https://doi.org/10.1038/s41541-020-0197-2
- Prasad U., 2020. COVID-19 mRNA Vaccine: A Milestone in Science and a Game Changer in Medicine. Posted on 29 December 2020. Scientific European. Available on https://www.scientificeuropean.co.uk/covid-19-mrna-vaccine-a-milestone-in-science-and-a-game-changer-in-medicine/ Accessed on 15 January 2021.