Genetic vaccines: strategies for optimization.

Vaccination with attenuated or killed microbes, purified or recombinant subunit proteins and synthetic peptides is often hampered by toxicity, the presence of infectious agents, weak immune responses and prohibiting costs, especially in the developing world. Such problems may be circumvented by genetic immunization which has recently emerged as an attractive alternative to conventional vaccines. Numerous studies have already shown that immunization of experimental animals with plasmid DNA encoding antigens from a wide spectrum of bacteria, viruses, protozoa and cancers leads to protective humoral and cell-mediated immunity. This review deals with the background and progress made so far with DNA vaccines and their theoretical and practical advantages as well as potential risks, discusses proposed mechanisms of DNA transfection of cells and induction of immune responses to the produced vaccine antigen, and evaluates strategies for the control and optimization of such responses.