A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

Abstract

This review provides a comparison of the theoretical issues and experimental findings for plasmid DNA and mRNA vaccine technologies. While both have been under development since the 1990s, in recent years, significant excitement has turned to mRNA despite the licensure of several veterinary DNA vaccines. Both have required efforts to increase their potency either via manipulating the plasmid DNA and the mRNA directly or through the addition of adjuvants or immunomodulators as well as delivery systems and formulations. The greater inherent inflammatory nature of the mRNA vaccines is discussed for both its potential immunological utility for vaccines and for the potential toxicity. The status of the clinical trials of mRNA vaccines is described along with a comparison to DNA vaccines, specifically the immunogenicity of both licensed veterinary DNA vaccines and select DNA vaccine candidates in human clinical trials.

Progress and Prospects on Vaccine Development against SARS-CoV-2

“…DNA vaccines are typically comprised of plasmid DNA molecules that encode one or more antigens. They are superior to mRNA vaccines in the formulations needed for stability and delivery efficiency, nevertheless they need to enter the nucleus that may bring in the risk of vctor integration and mutations in the host genome [48]. So far, two SARS-CoV-2 DNA vaccines are under development.…”

Therapeutic Vaccine in Chronically HIV-1-Infected Patients: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Trial with HTI-TriMix

“…Even though, in a recent overview of prophylactic and therapeutic DNA and mRNA vaccine studies, it was shown that in some studies, up to 78% of vaccinated subjects experienced adverse events, amongst which 10% were of grade 3. None of the discussed trials that involved mRNA have reached phase 3 research stages yet [27]. Follow-up was given to the notification of the erroneous study product following good clinical practice guidelines, amongst which were notification of participants, competent authorities and institutional review boards.…”

Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives

“…Besides the general advantages of mRNA, previously mentioned, this active substance shows specific interesting features for immunotherapy: The immunostimulatory capacity, although it can also have potential toxicity, the transient nature of the antigen and the versatility of applications, including prophylaxis, therapy and personalized vaccines [164,165]. Several preclinical studies of mRNA vaccines are showing promising perspectives.…”

“…However, the preclinical and human immunogenicity is not always the same, animal studies are not predictive of human efficacy, and there is a lack of knowledge about the targets and type of immune responses which are essential for effective therapy. These challenges highlight the need to carry out further studies on the correlation between the immune response mechanisms in animals and in humans, as well as of a better understanding of the diseases to be treated or prevented, for the clinical success of immunotherapy [14,165].…”

“…Figure 4 shows a representative scheme of the intracellular disposition of these two types of vaccines; in both cases the translation machinery of the cell is used to produce the specific antigen [13]. between the immune response mechanisms in animals and in humans, as well as of a better understanding of the diseases to be treated or prevented, for the clinical success of immunotherapy [14,165].…”