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 eith er individual or a collection of antigens is directly administered to a hos t. Such immunization leads to host expression of the delivered foreign gene , resulting in the induction of a specific immune response against the in v ivo produced antigen. DNA immunization has been shown to induce protective immune responses in several infectious disease and cancer experimental mode l systems. Furthermore, DNA vaccines have recently entered the clinic for a nalysis as both prophylactic and therapeutic agents. Although the mechanism s of immunity to DNA have not yet been fully elucidated, it has become appa rent that the immune response achieved by DNA vaccination is quite malleabl e, and can be manipulated by altering the conditions under which the vaccin e is administered. Either through changing the method or location of immuni zation, altering the number of immunostimulatory sequences in the plasmid, altering the immunization regimen, or coadministering genes for cytokines o r costimulatory molecules, one can modulate both the magnitude and orientat ion of the subsequent immune response. Through maximization of this feature of DNA immunization, we will likely be able to design vaccines and immunot herapeutic agents that are tailored to the correlates of protection for a p articular disease, resulting in a new generation of more focused and effect ive immune stimulating agents.