DNA vaccines: ready for prime time?

Abstract

Since the initial discovery, over a decade and a half ago, that genetically engineered DNA can be delivered in vaccine form and can elicit an immune response, there has been a great deal of progress in understanding the basic biology of this platform. Data from preclinical studies using DNA vaccine technology has generated a large amount of excitement, because protective immunity was induced by platforms against a broad range of virus families. The initial development of DNA vaccines in larger animals and human studies showed that DNA is well tolerated and has an excellent safety record. Clinical studies of first-generation vaccines, primarily consisting of naked DNA, showed that this platform induces only low levels of immunity. The status of these vaccines as a stand-alone platform was thus jeopardized, demonstrating the need for improvements in delivery technology and continued optimization of 'prime-boost' strategies. Recent studies have generated new leads from basic research on insert design, RNA structure, variation in codon usage, and leader-sequence optimizations — all of which improve the immune potency of DNA vaccines. New formulations, including lipids and polymers, and new delivery devices, including the gene gun, skin-delivery devices and, most recently, electroporation technology, seem to be promising in preclinical models and will be followed closely in the clinic. Strong molecular adjuvants that are included in plasmid formulations seem to be important and are particularly well suited for further improving immune potency of DNA vaccines and for controlling the phenotype of the induced immune response. In the past 3 years, four DNA vaccine or immune therapy products have been licensed in the veterinary arena for diverse species, including salmon, pigs, dogs and horses. These products are the first validation of the commercial viability of the DNA vaccine platform and illustrate strong progress in this area. Progress in the DNA platform will continue to be an exciting and highly productive adventure, illustrating the best in academic and translational science and cooperation between industry, the regulatory authorities, funding agencies and academicians.