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-galacto sidase, a cytoplasmic antigen, delivered as plasmid DNAs. We found tha t cytokines characteristic of a Th1 phenotype are produced in mice imm unized by these plasmid DNAs. Using repeated injections of low doses o f purified antigen, we demonstrated that neither prolonged presence of the antigen nor site of immunization resulted in an immune response w ith characteristics resembling those obtained with DNA-mediated immuni zation. Analysis of immune responses induced in mice by coinjection of plasmid DNA and beta-galactosidase or HBsAg demonstrated that the coi njected DNA stimulated a Th1 response against the injected antigen. Th ese data therefore strongly suggest that the strong immune response ob tained after intramuscular DNA immunization was due to the adjuvant ef fect of the plasmid DNA which is also responsible for the selective ac tivation of CD4(+) T cells with a Th1 phenotype. (C) 1997 Academic Pre ss.