Nucleic acid vaccines - Tasks and tactics

There are no adequate vaccines against some of the new or reemerged infecti ous scourges such as HIV and TB. They may require strong and enduring cell- mediated immunity to be elicited. This is quite a task, as the only known b asis of protection by current commercial vaccines is antibody. As DNA or RN A vaccines may induce both cell-mediated and humoral immunity, great intere st has been shown in them. However, doubt remains whether their efficacy wi ll suffice for their clinical realization. We look at the various tactics t o increase the potency of nucleic acid vaccines and divided them broadly un der those affecting delivery and those affecting immune induction. For deli very, we have considered ways of improving uptake and the use of bacterial, replicon or viral vectors. For immune induction, we considered aspects of immunostimulatory CpG motifs, coinjection of cytokines or costimulators and alterations of the antigen, its cellular localization and its anatomical l ocalization including the use of ligand-targeting to lymphoid tissue. We al so thought that mucosal application of DNA deserved a separate section. In this review, we have taken the liberty to discuss these enhancement methods , whenever possible, in the context of the underlying mechanisms that might argue for or against these strategies.