Plasmid vector design and technologies for DNA vaccine development

Nucleic-acid based DNA vaccines represent a novel class ofbiodrugs with great therapeutic potential as competitive alternativeapproach to conventional protein vaccines both as prophylacticand therapeutic treatment of infectious diseases, cancerand allergy. Despite safety concerns have been overcome, lowimmunogenicity profiles of DNA vaccines has hindered theirprogress in humans. DNA vaccines need to make up for thislimitation by altering plasmid construction through complementaryvector design innovations that, in combination withimproved delivery platform, may enhance DNA vaccine performanceand clinical outcomes. DNA vaccination platform takesadvantage of in vivo processes and has the potential to harnessthe full power of the immune system, through engagement ofmultiples routes to activate both branch of the immune system(i.e. innate immunity as well as adaptive immunity). Currentknowledge of the molecular and immunological mechanisms bywhich DNA vaccines work can be used to bring about improvementsin their efficacy. Advanced technologies such asimmunoinformatics (i.e. in silico prediction of potential T cellepitopes), antigen/epitope optimisation and expression, provisionof CD4 T cell help, intracellular antigen targeting ensuringefficient MHC I and MHC II compartment addressing, inclusionof genetic adjuvants have been applied to improve the efficacy ofDNA vaccines. In order to translate these approaches into atherapeutic strategy, we have developed a series of modular antiidiotypicDNA vaccines and have assessed the induction of antitumorimmunity in an aggressive murine B-cell lymphomamodel. Here we report that the DNA vaccine variants, in combinationwith electroporation delivery platform, are suitable toengage both humoral and cellular immune responses, thus resultingin efficacious DNA vaccines performance.