A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

Liu, Margaret A.

Plasmid DNA was shown to be effective for stimulating CTLs that were capable of protecting mice against influenza caused by a strain different from the strain from which the encoded antigen was derived [7, 27, 28] . Because the plasmid DNA, when injected intramuscularly (i.m.), primarily transduced muscle cells rather than professional Antigen Presenting Cells (APCs), the mechanism whereby MHC Class I-restricted CTLs were generated needed explaining. It was found that cross-priming appeared to be a key mechanism for generating CTLs following DNA vaccine immunization, as directly demonstrated by experiments with chimeric mice using bone-marrow derived dendritic cells [27] , and because muscle cells were the only cells observed to translate the protein encoded by directly-injected plasmid DNA [6, 29] . The efficacy in pre-clinical models raised the hopes that such plasmid DNA-based CTL-inducing vaccines could be developed that would be protective against multiple strains of HIV or influenza [7, 30] (so as to produce a "universal" flu vaccine). Currently, existing influenza vaccines depend upon strain-specific antibodies, which result in strain-specific or strain-limited protection. Similarly, mRNA delivered in liposomes was shown early on to be capable of inducing CTLs [9] . The uptake of the mRNA is also mainly by non-immune cells, including muscle cells [31] .