DNA Vaccines

Abstract

DNA vaccines are bacterial plasmids capable of expressing a protein antigen following injection into the host. They differ from traditional vaccines in that the antigen or pathogen itself is not directly injected or inoculated. Rather the plasmids utilize a promoter which is active in mammalian cells, generally a viral promoter to drive the expression of a gene encoding the antigen of interest. This gene can be taken from the pathogen or tumor or may be a cDNA version of the gene in the case of RNA viruses. These vaccines have been shown to generate antibody responses and cellular immunity, including T cell help and cytotoxic T lymphocytes (CTL), as well as protection from infectious or tumor challenge in a variety of pre-clinical models of disease₁. DNA vaccines can generate neutralizing antibodies and prime for boosting by the analogous protein antigen (either recombinant or purified) as well_2,3. These antibody responses have been shown to protect in a variety of disease models such as in a mucosal model of HSV₄, in a rabbit model of papilloma virus₅, and in a murine model of influenza. The ability to generate MHC Class I-restricted CTL directed against epitopes from conserved internal viral proteins, for example, was demonstrated, in the initial proof-of-concept experiments for DNA vaccines, to provide cross-strain protection from viral challenge₆. That is, utilizing a gene encoding nucleoprotein from one subtype of influenza (H1N1), a DNA vaccine could generate CTL which protected mice against challenge with a different subtype of influenza (H3N2).