A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

Liu, Margaret A.

As noted earlier, one company initially highlighted a focus on therapeutic disease areas but reprioritized vaccines, possibly due to the recognition of the low amount of antigen actually produced by the mRNA coupled with the low amounts of protein needed for vaccines because of the amplification by the immune system, possibly as a response to emerging diseases such as the Zika epidemic, and possibly influenced by the liver toxicity seen in their pre-clinical studies [59] for delivering even the low amounts of mRNA needed for the disease (Crigler-Najjar, see above). Lipid nanoparticles are also used for that company's vaccine formulations, although it is not known how these relate to the formulation used for Crigler-Najjar (the company has published relatively little in the peer-reviewed scientific literature related to their clinical trials). References, when available, are provided within the table, although in some cases, the assumption is made that the pre-clinical construct in the reference is the same construct (antigen) as the one in the clinical trial. Table 4 lists clinical trials of mRNA for additional applications. Data are taken from clinicaltrials.gov in addition to the citations listed. Table 4 excludes studies that employ cells transfected ex vivo prior to re-administration to patients and excludes those that supply mRNA encoding immunomodulators without a specific antigen also being provided.