A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

Liu, Margaret A.

For many vaccines, antibodies play a key role in protection. The cell that is transfected by the plasmid DNA or the mRNA vaccine does not have to be a professional antigen presenting cell (APC) in order to produce the antigenic protein that stimulates B cells. Cellular immune responses, notably CTLs, are thought to be important for tumor immunotherapy as well as to potentially play a role in protection against certain infectious diseases, e.g., tuberculosis (Tb), HIV, and malaria, or for vaccines effective against multiple strains of a virus, such as influenza, even though CTLs alone would not provide sterilizing immunity. In order for a vaccine to generate MHC Class I-restricted CTLs, the antigen either needs to be produced inside a professional APC or by a cell from which antigen can be cross-presented by an APC to then stimulate CTLs. The most direct way to ensure delivery of the gene encoding an antigen to a professional APC is to transfect the cells in vitro prior to administering the transfected cells back to the patient. Indeed, the largest number of mRNA clinical trials currently underway, notably for cancer immunotherapy, involve the ex vivo transfection of cells with mRNA encoding tumor antigens followed by re-infusion of the transfected cells into the patient. Because this is a more cumbersome process for making a product than having a non-personalized product in a vial, direct administration of the plasmid DNA or the mRNA to a patient is preferable for convenience, cost, and time.