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13 Delivery Systems and Adjuvants for DNA Vaccines

Jeffrey B. Ulmer, Margaret A. Liu


The expression of antigens by host cells is an effective means of antigen presentation by major histocompatibility complex (MHC) class I molecules leading to the induction of cytotoxic T lymphocyte (CTL) responses. This can be accomplished by the infection of cells with pathogens, such as viruses, or by the transduction of cells with live recombinant vectors or plasmid DNA. The impetus to consider using plasmid DNA for the purpose of vaccination was suggested by two papers that demonstrated protein expression in situ after the administration of plasmid DNA. Benvenisty and Reshef (1986) showed that calcium phosphate precipitated DNA encoding reporter genes and hormones inoculated intraperitoneally in mice resulted in expression. Wolff et al. (1990) administered plasmid DNA encoding reporter genes, such as luciferase and β-galactosidase, by various routes and found reporter protein expression in the tissues injected. However, expression in myocytes after intramuscular (i.m.) injection yielded the highest levels. This expression was subsequently shown to be long-lived (Wolff et al. 1992a), despite the fact that the plasmid remained episomal (Wolff et al. 1992a; Nichols et al. 1995). These observations led several groups of researchers to investigate plasmid DNA inoculation as a potential vaccine strategy. In 1992, the induction of antibody responses was observed by Tang et al. (1992) using a gene gun to deliver DNA-coated gold beads into skin cells. In 1993, the induction of CTL responses by a DNA vaccine was first reported by Ulmer et al. (1993) after the i.m. injection of DNA encoding influenza nucleoprotein...

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