Since that time, there has since been much progress in understanding the basic biology behind this deceptively simple vaccine platform and much technological advancement to enhance immune potency. Among these advancements are improved formulations and improved physical methods of delivery, which increase the uptake of vaccine plasmids by cells; optimization of vaccine vectors and encoded antigens; and the development of novel formulations and adjuvants to augment and direct the host immune response. The ability of the current, or second-generation, DNA vaccines to induce more-potent cellular and humoral responses opens up this platform to be examined in both preventative and therapeutic arenas. This review focuses on these advances and discusses both preventive and immunotherapeutic clinical applications.
Current licensed vaccines are predominantly composed of either killed pathogens, pathogen subunits, or live-attenuated viruses. Nonlive vaccines, which confer protection primarily through the induction of CD4+ T- cell and humoral mechanisms, generally do not provide life-long immunity. In contrast, live-attenuated vaccines can mobilize both the cellular and humoral arms of the immune response and generally induce more-prolonged immunity. However, their degree of attenuation can significantly lower the immunogenicity of live vaccines, and the development of live vaccine strategies can be especially challenging when the goal is to target multiple viral subtypes or pathogens. There are also theoretical safety concerns associated with the use of both nonlive and attenuated approaches. These limitations continue to drive the need to develop new vaccine platforms that offer broader immunogenicity.
DNA vaccines first sparked the interested of the scientific community in the early 1990s, when it was reported that plasmid DNA, delivered into the skin or muscle, induced antibody responses to viral and nonviral antigens [1–4]. The simplicity and versatility of this vaccine approach generated a great deal of excitement and inspired additional preclinical studies targeting a plethora of viral and nonviral antigens. In theory, DNA vaccines could generate broad immune responses, similar to the live-attenuated virus platform, without the need for a replicating pathogen.