The most revolutionary approach to vaccination is the introduction into the vaccinee of DNA encoding an antigen, with the aim of inducing cells of the vaccinee to synthesize the antigen. One advantage of this approach is that there is a steady supply of new antigen to stimulate the immune system, as with live virus vaccines. Because the antigen (a virus protein in this case) is produced within the cells of the vaccinee, it is likely to stimulate efficient T-cell-mediated responses.
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Figure 24.5 Production of a DNA vaccine. The virus protein gene is inserted into a plasmid, which is then cloned in bacteria. The plasmid is extracted from the bacterial cells, purified and incorporated into a vaccine.
A procedure for the production of a DNA vaccine is outlined in Figure 24.5. The antigen-encoding sequence, obtained directly from a DNA virus or by reverse transcription from an RNA virus, is inserted into a plasmid between a strong promoter and a poly(A) signal. The plasmid is replicated in bacterial cells and is then purified for use as a vaccine. Administration of the vaccine can be by injection into a muscle or by using a gene gun that delivers DNA-coated gold beads directly into skin cells.
Experimental DNA vaccines have been produced for a number of viruses, including HIV-1, SARS coronavirus, West Nile virus and foot and mouth disease virus; trials have been carried out in mice, pigs, horses and humans. Before any DNA vaccine goes into clinical use some important questions about safety must be answered. There must be confidence that injection of the DNA will not trigger an anti-DNA autoimmune disease, and that the DNA will not create cancer-causing mutations by insertion into host genomes.
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