A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

Liu, Margaret A.

When DNA vaccines initially entered into human clinical trials, concern was raised about the theoretical possibility of them causing autoimmunity or that the DNA would integrate into the genome. The rationale for concerns about autoimmunity was that anti-DNA antibodies are a hallmark of various autoimmune diseases. To date, both pre-clinical testing and careful clinical monitoring have shown DNA vaccines to not induce or to worsen auto-immunity, and in fact, human clinical trials employing DNA vaccines for therapy of two autoimmune diseases (diabetes mellitus and multiple sclerosis) gave encouraging results in human clinical trials for a therapeutic benefit of the DNA vaccines [47, 62] . For mRNA, a proposed mechanism for possible autoimmune responses is via the induction of type I interferon [63] , which may result in both inflammation and possibly autoimmune responses [64] . This includes work showing that the responses seen in mice were similar to those seen in humans for an influenza mRNA vaccine construct via TLR7 and TLR8 in humans and via cytoplasmic RNA sensors in both mice and humans [65] .