A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

Liu, Margaret A.

In summary, despite all the excitement over pre-clinical efficacy of mRNA, it should be remembered that in many ways, the mRNA field is recapitulating what occurred with plasmid DNA 20+ years ago, when seemingly almost any disease could be prevented or treated in pre-clinical animal disease models with the administration of an unformulated plasmid encoding a key antigen [1] . Therefore, one must keep in mind that pre-clinical immunogenicity or even protection/therapy, and human immunogenicity are low hurdles and are not predictive of human efficacy. One reason this is so challenging is that, for many of the diseases under evaluation, scientists do not know which immune response or combination of immune responses and which antigen targets are the crucial elements for efficacy; the vaccine technology alone is not the only piece of the puzzle. Table 5 summarizes the main advantages and disadvantages of mRNA vaccines with a comparison to DNA vaccines. Generic manufacturing process (as with DNA vaccines) 3)