A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

Liu, Margaret A.

Lower quantities of the (antigenic) protein are presumably needed for vaccines (due to amplification of the immune response against the antigen) compared to amounts of protein that might be needed for therapeutic disease targets. Additionally, whereas for gene therapy, where long-lasting or even permanent production of the therapeutic protein is desired, vaccines likely benefit from the transient nature of the antigen (followed by boosting). This is because, for example, the development of high affinity antibodies occurs as antigen becomes scarcer. Subsequent boosts with antigen then expand the production of these high affinity antibodies. The relatively temporary nature and presumably small amounts of protein produced by mRNA would fit with this paradigm if the mRNA is present in great enough quantities, persists, and is active long enough to produce sufficient amounts of protein antigen to stimulate the desired immune responses. DNA vaccines likewise have been demonstrated to produce the encoded protein for a limited period of time, although this is likely longer than mRNA constructs given the greater inherent stability of plasmid DNA compared to mRNA. Plasmid DNA has been shown to persist in muscle up to six months in a non-integrated fashion [18] .