A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

Liu, Margaret A.

In addition to the various diseases for which DNA vaccines used alone have resulted in promising human clinical immune responses, in a variety of clinical trials for several other diseases, such as HIV, plasmid DNA as a prime followed by a heterologous boost has resulted in significant potency for the generation of immune responses, including CTLs. Additionally, as mentioned above, phase II studies for the treatment of two autoimmune diseases, diabetes and multiple sclerosis, yielded encouraging clinical responses, which may mechanistically be due in part to the design of the vectors to avoid the Th1 cell responses that generally are seen with the plasmids utilized for other diseases [47] . Moreover, clinical trials of DNA vaccines for cancer therapy utilizing electroporation have provided encouraging results, including for CIN3 (cervical carcinoma in situ 3) [86] and CIN2/3 [87] as well as for head and neck cancer [88] , which are all related to human papillomavirus (HPV) infection. Other clinical trials of DNA vaccines for cancer have included using DNA that encoded fusion proteins including a tumor CTL epitope(s) and a T helper stimulator(s) [89] [90] [91] . Therefore, even though no human DNA vaccines have been licensed, the existing data have provided evidence for immunogenicity and early stage evidence of clinical effect in humans for certain antigens/diseases as well as efficacy in animals ranging from fish to horses. The remainder of this special issue deals with these efforts and ongoing clinical trials, thus they are not elaborated upon here.