Figure 1. DNA vaccines: optimization strategies to enhance immunogenicity.
DNA vaccine technology has been the target of ongoing efforts to optimize the platform to increase antigen expression and vaccine immunogenicity (see main text for a detailed explanation of each step). There are currently several ways in which antigen expression and immunogenicity can be improved for the DNA vaccine platform. These include: optimization of the transcriptional elements on the plasmid backbone (1); strategies to improve protein expression of the gene of interest (2), including factors to avoid (for example, chi-sites, which are sequences that encourage crossing-over to occur at that site); inclusion of formulation adjuvants (3) or immune plasmid adjuvants (4); and the use of next-generation delivery methods (5). Several formulations have been developed and are being testing at all stages of preclinical and clinical development for their ability to enhance antigen expression and immunogenicity. These mechanisms include encapsulation and protection of DNA from extracellular degradation through to particle trapping and high-velocity delivery, with the ultimate goal of introducing the plasmid directly into the cytosol of target cells. In addition, immune adjuvant classes that encode immune modulatory molecules that target death receptors, growth factors, adhesion molecules, cytokines and chemokines as well as Toll receptor ligands exist. It should be noted that many of these plasmid optimization and formulation strategies, as well as the adjuvant systems, are used in combination with novel delivery mechanisms that result in an overall enhanced vaccine platform.