Modulating the immune response to genetic immunization.

Genetic immunization, also known as DNA or polynucleotide immunization, is a novel strategy for vaccine development in which plasmid DNA encoding either individual or a collection of antigens is directly administered to a host. Such immunization leads to host expression of the delivered foreign gene, resulting in the induction of a specific immune response against the in vivo produced antigen. DNA immunization has been shown to induce protective immune responses in several infectious disease and cancer experimental model systems. Furthermore, DNA vaccines have recently entered the clinic for analysis as both prophylactic and therapeutic agents. Although the mechanisms of immunity to DNA have not yet been fully elucidated, it has become apparent that the immune response achieved by DNA vaccination is quite malleable, and can be manipulated by altering the conditions under which the vaccine is administered. Either through changing the method or location of immunization, altering the number of immunostimulatory sequences in the plasmid, altering the immunization regimen, or coadministering genes for cytokines or costimulatory molecules, one can modulate both the magnitude and orientation of the subsequent immune response. Through maximization of this feature of DNA immunization, we will likely be able to design vaccines and immunotherapeutic agents that are tailored to the correlates of protection for a particular disease, resulting in a new generation of more focused and effective immune stimulating agents.