Immunology of DNA vaccines: CpG motifs and antigen presentation

DNA vaccines elicit high levels of specific cytotoxic T lymphocytes and antibody production in numerous animal models. However, the specific immunological events which lead to this effective immune response remain unclear. Presentation of DNA-encoded antigens is particularly intriguing as there is now evidence to suggest that this occurs via both endogenous intracellular and cross-presentation. Further, it has been observed that many plasmid DNA vectors used in DNA vaccination contain CpG motifs--sequences of bacterial DNA which induce pro-inflammatory cytokines in various cells--and which thus provide a novel adjuvant for injected antigens. In this review we will discuss the effects these bacterial DNA sequences have on cells of the immune system, the immune response generated after DNA vaccination and the mechanisms by which DNA-encoded antigens are likely to be presented.