A blueprint for DNA vaccine design.

Although safety concerns have been overcome, lower immunogenicity profiles of DNA vaccines have hindered their progress in humans. DNA vaccines need to make up for this limitation by altering plasmid construction through vector design innovations intended for enhancement of transgene expression and immunogenicity. The next-generation vectors also address safety issues such as selection markers. This chapter discusses (a) plasmid backbone design, (b) enhancement of antigenic protein expression and immunogenicity, and (c) vector modification to increase innate immunity. Modifications of the basic design, when combined with improved delivery devices and/or prime/boost regimens, may enhance DNA vaccine performance and clinical outcomes.