Prospects for control of emerging infectious diseases with plasmid DNA vaccines

Moss, Ronald B

Overall, a well-tolerated safety profile has been observed in human clinical trials of DNA vaccination [10] . Early in the development, there were numerous theoretical safety concerns regarding DNA vaccines. In particular, there were concerns about the fate of the injected genes and the potential for insertion into the host DNA possibly result- ing in the uncontrolled stimulation of other genes such as those that may cause cancer. These concerns have dissipated over the years based on thousands of human subjects who have undergone DNA vaccination or plasmidbased gene therapy. Furthermore, in pre-clinical safety studies in animals, the potential for plasmid integration into the host genome has been shown to be negligible and several orders of magnitude below the spontaneous mutation rate that occurs naturally in mammalian genes [11] . There were also early concerns regarding the induction of autoimmune reactions, as DNA may be considered as a self antigen to the host. Increased rates of autoimmunity or anti-DNA antibodies such as those observed in Systemic Lupus Erythematosis have not been observed in clinical trials of DNA vaccination [12] . Interestingly, as plasmid DNA vaccines are noninfectious, significant immune responses are not developed against the plasmid itself. Therefore only specific immune responses to the expressed antigen are stimulated with this approach. In contrast, with viral vectors such as adenoviruses, pre-existing and post vaccination immunity to the vector itself can be generated thereby limiting the pathogen specific immune response In contrast, DNA vaccination can be repeated without diminishing the specific immune response. This may be a pertinent beneficial aspect of DNA immunization, particularly in light of recent clinical trials in humans using viral vector-based vaccines, such as the common cold adenovirus, where immunity to the vector itself has been raised as a potential safety issue [13, 14] . In summary, the potential risks of DNA vaccines appear to be minimal based on safety data from human clinical trials in thousands of subjects.