Revealing the potential of DNA-based vaccination: Lessons learned from thehepatitis B virus surface antigen

DNA-based vaccination is a novel technique to efficiently stimulate humoral (antibody) and cellular (T cell) immune responses to protein antigens. In DNA-based vaccination, immunogenic proteins are expressed in in vivo transf ected cells of the vaccine recipients in their native conformation with cor rect posttranslational modifications from antigen-encoding expression plasm id DNA, This ensures the integrity of antibody-defined epitopes and support s the generation of protective (neutralizing) antibody titers. Plasmid DNA vaccination is furthermore an exceptionally potent strategy to stimulate CD 8(+) cytotoxic T lymphocyte (CTL) responses because antigenic peptides are efficiently generated by endogenous processing of intracellular protein ant igens. These key features make DNA-based immunization an attractive strateg y for prophylactic and therapeutic vaccination against extra- and intracell ular pathogens. In this brief review, we summarize the current state of exp ression vector design, DNA delivery strategies, priming immune responses to intracellular or secreted antigens by DNA vaccines and unique advantages o f DNA- versus recombinant protein-based vaccines using the hepatitis B surf ace antigen (HBsAS) as a model antigen.