A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

Liu, Margaret A.

DNA vaccines did not need to be evaluated by the US National Institutes of Health (NIH) Recombinant Advisory Committee prior to human clinical trials, unlike viral vectors for gene therapy. Nevertheless, significant safety studies were initially required to evaluate the possibility of integration of the plasmid DNA into the host genome. As a result of these studies for both human vaccines [18, 66] and for the licensed DNA vaccines for fish [67] , as well as the many human studies with DNA vaccines that have demonstrated safety, little concern now exists regarding integration. Comparisons have stated that mRNA offers an advantage because RNA itself cannot integrate into genomic DNA without the presence of the viral elements in a retrovirus that enable such integration (reverse transcriptase and integrase). However, HERVs [68] (human endogenous retroviruses) whose remnants are now permanent parts of human genomes as retrovirus-like sequences comprise up to 8% of the human genome. In addition, some recipients of mRNA drugs or vaccines may be already infected with a retrovirus (e.g., HIV), thus providing a theoretical means for provision of the proteins needed for integration [69, 70] . Nevertheless, the risk of integration remains, at this point, extremely unlikely for mRNA, even from a theoretical standpoint, nor is it any longer a significant concern for plasmid DNA. This means that mRNA does not offer any clear advantage compared to plasmid DNA in this regard. From a regulatory perspective, mRNA prophylactic vaccines appear to not be considered gene therapy products [71] , similar to DNA vaccines before them.