Plasmid vector design and technologies for DNA vaccine development

Nucleic-acid based DNA vaccines represent a novel class of biodrugs with great therapeutic potential as competitive alternative approach to conventional protein vaccines both as prophylactic and therapeutic treatment of infectious diseases, cancer and allergy. Despite safety concerns have been overcome, low immunogenicity profiles of DNA vaccines has hindered their progress in humans. DNA vaccines need to make up for this limitation by altering plasmid construction through complementary vector design innovations that, in combination with improved delivery platform, may enhance DNA vaccine performance and clinical outcomes. DNA vaccination platform takes advantage of in vivo processes and has the potential to harness the full power of the immune system, through engagement of multiples routes to activate both branch of the immune system (i.e. innate immunity as well as adaptive immunity). Current knowledge of the molecular and immunological mechanisms by which DNA vaccines work can be used to bring about improvements in their efficacy. Advanced technologies such as immunoinformatics (i.e. in silico prediction of potential T cell epitopes), antigen/epitope optimisation and expression, provision of CD4 T cell help, intracellular antigen targeting ensuring efficient MHC I and MHC II compartment addressing, inclusion of genetic adjuvants have been applied to improve the efficacy of DNA vaccines. In order to translate these approaches into a therapeutic strategy, we have developed a series of modular antiidiotypic DNA vaccines and have assessed the induction of antitumor immunity in an aggressive murine B-cell lymphoma model. Here we report that the DNA vaccine variants, in combination with electroporation delivery platform, are suitable to engage both humoral and cellular immune responses, thus resulting in efficacious DNA vaccines performance.