The ability of DNA vaccines to provide effective immunological protection against infection and tumors depends on their ability to generate good CD4+ and CD8+ T-cell responses. Priming of these responses is a property of dendritic cells (DCs), and so the efficacy of DNA-encoded vaccines is likely to depend on the way in which the antigens they encode are processed by DCs. This processing could either be via the synthesis of the vaccine-encoded antigen by the DCs themselves or via its uptake by DCs following its synthesis in bystander cells that are unable to prime T cells. These different sources of antigen are likely to engage different antigen-processing pathways, which are the subject of this review. Understanding how to access different processing pathways in DCs may ultimately aid the rational development of plasmid-based vaccines to pathogens and to cancer.
