Nucleic acid adjuvants: toward an educated vaccine

Two striking facts surround the practice of vaccination: It is the sole medical approach to have fully annihilated a disease, yet the development of most effective vaccines took place without considering the intricate cellular processes they wish to effectuate. While extremely potent vaccines have been developed that can protect practically a lifetime after a single dose, numerous other vaccines have utterly failed or provide only marginal protection. Here, we aim to illustrate why this difference in efficacy exists, and underline why specific cytotoxic T cell-inducing vaccines could combat persistent major diseases. Moreover, we discuss how the combinatorial use of nucleic acid adjuvants in vaccines could aid the development of the latter and move vaccine design from the empirical stage into an era of "educated design."