The preferential induction of a Th1 immune response by DNA-based immunization is mediated by the immunostimulatory effect of plasmid DNA.

In the present study, we have investigated the T cell response to the HBsAg, normally secreted as multivalent particles, and to beta-galactosidase, a cytoplasmic antigen, delivered as plasmid DNAs. We found that cytokines characteristic of a Th1 phenotype are produced in mice immunized by these plasmid DNAs. Using repeated injections of low doses of purified antigen, we demonstrated that neither prolonged presence of the antigen nor site of immunization resulted in an immune response with characteristics resembling those obtained with DNA-mediated immunization. Analysis of immune responses induced in mice by coinjection of plasmid DNA and beta-galactosidase or HBsAg demonstrated that the coinjected DNA stimulated a Th1 response against the injected antigen. These data therefore strongly suggest that the strong immune response obtained after intramuscular DNA immunization was due to the adjuvant effect of the plasmid DNA which is also responsible for the selective activation of CD4(+) T cells with a Th1 phenotype.