DNA vaccines: a review of developments.

Immunisation with purified DNA is a powerful technique for inducing immune responses. The concept is very simple, involving insertion of the gene encoding the antigen of choice into a bacterial plasmid, and injection of the plasmid into the host where the antigen is expressed and induces humoral and cellular immunity. This technology can induce immunity to all antigens that can be encoded by DNA; this includes all protein, but not carbohydrate, antigens. DNA immunisation appears to result in presentation of antigens to the host's immune system in a natural form, similar to that achieved with live attenuated vaccines. The most efficacious routes for DNA immunisation are bombardment with particles coated with DNA (gene-gun), followed by intramuscular and intradermal administration. The efficiency of transfection of host cells is low, but sufficient to induce immunological responsiveness. The DNA plasmid is retained in the transfected cells in an unintegrated form for the life of the cell. The majority of transfected cells are eliminated, but residual expression has been detected for longer periods. In animal model systems, DNA immunisation has been shown to induce protective immunity to influenza, herpes, rabies, hepatitis B and lymphocytic choriomeningitis viruses, and to malaria and mycobacteria. However, strategies to induce protective immunity to HIV and other disease agents remain to be developed. DNA vaccines permit modulation of the immune response by altering the route or method of DNA administration, by including immunostimulatory sequences in the plasmid, and by co-administration of cytokine genes with the gene encoding the antigen of interest. A T helper 1 response provides cell-mediated immune killing of infected cells and neutralising antibody production, while a T helper 2 response induces IgE and allergic responses. The advantages of DNA immunisation are: similarity to live attenuated vaccination but without the possibility of contamination with undesirable agents;correct presentation of antigen;combinations of DNA-encoded antigens and/or cytokines may be administered;genetic stability;potential speed of making new vaccines with genetic identity;development of vaccines for agents that cannot be grown in culture;no need for a cold chain; andpossibility of modulation of the immune response. The perceived risks include: integration of the plasmid into the host genome;induction of anti-DNA antibodies and autoimmunity; andinduction of tolerance. The available information concerning safety is encouraging, with the risk of integration being considered to be orders of magnitude below the spontaneous mutation frequency in humans. DNA immunisation offers the possibility of extending the control of infectious diseases far beyond those that are currently controlled by conventional and recombinant vaccines, to include vaccines for parasites and cancer. However, it is currently too early to predict the future extent of use of DNA vaccines in human immunisation programmes because the initial clinical trials are still in progress.