Plasmids genetic vaccines

Liu MA, Ulmer JB (2005) Human clinical trials of plasmid DNA vaccines. Adv Genet 55 25-40... 

Anwer, K., Earle, K.A., Shi, M., Wang, J., Mumper, R.J., Proctor, B. et al. (1999) Synergistic effect of formulated plasmid and needle-free injection for genetic vaccines. Pharm. Res., 16, 889-895. 

DNA plasmid-based treatment ( gene therapy ) is considered an alternative to the one based on classical chemical drugs or proteins recovered from recombinant cells. Treatment of acquired and inherent genetic diseases as well as the use of DNA for the purpose of vaccination are potential applications of plasmid DNA (pDNA). The plasmid carries information that allows protein expression in the targeted human cells as well as eukaryotic regulatory elements and specific prokaryotic sequences that control replication in the host cell, see Fig. 10. Formulation is required for ex- or in-vivo administration. Selected systems for gene expression can be viral or non-viral. 

The field of DNA vaccines centers on the ability to deliver genetic material, coding, for desired protein antigens in the context of a mammalian expression vector (Donnelly et al., 1997). It was realized that the immunostimulatory properties observed with DNA vaccines, namely the ability to induce a Thl biased or cell mediated immune response, was attributable in part to the presence of CpG motifs within the plasmid DNA (Klinman et al., 1997). In fact, it was demonstrated that the quality of immune activation by DNA vaccines could be influenced by the deliber-ate alteration of CpG content (Krieg et al., 1998). Further, with the identification of neutralizing CpG motifs it became possible to remove any neutralizing influence from the DNA vaccine plasmids. The end result was the optimization of DNA vaccine plasmids, with respect to immune activation (Krieg et al., 1998). 

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