VACCINATION WITH TRYPOMASTIGOTE SURFACE-ANTIGEN 1-ENCODING PLASMID DNA CONFERS PROTECTION AGAINST LETHAL TRYPANOSOMA-CRUZI INFECTION

DNA vaccination was evaluated with the experimental murine model of Tr ypanosoma cruzi infection as a means to induce antiparasite protective immunity, and the trypomastigote surface antigen 1 (TSA-1), a target of anti-T. cruzi antibody and major histocompatibility complex (MHC) c lass I-restricted CD8(+) cytotoxic T-lymphocyte (CTL) responses, was u sed as the model antigen. Following the intramuscular immunization of H-2(b) and R-2(d) mice with a plasmid DNA encoding an N-terminally tru ncated TSA-1 lacking or containing the C-terminal nonapeptide tandem r epeats, the antibody level, CTL response, and protection against chall enge with T. cruzi were assessed. In H-2(b) mice, antiparasite antibod ies were induced only by immunization with the DNA construct encoding TSA-1 containing the C-terminal repeats. However, both DNA constructs were efficient in eliciting long-lasting CTL responses against the pro tective H-2K(b)-restricted TSA-1(515-522) epitope, In H-2(d) mice, ino culation with either of the two TSA-1-expressing vectors effectively g enerated antiparasite antibodies and primed CTLs that lysed T. cruzi-i nfected cells in an antigen-specific, MHC class I-restricted, and CD8( +)-T-cell dependent manner. When TSA-1 DNA-vaccinated animals were cha llenged with T. cruzi, 14 of 22 (64%) H-2(b) and 16 of 18 (89%) H-2(d) mice survived the infection. The ability to induce significant murine anti-T. cruzi protective immunity by immunization with plasmid DNA ex pressing TSA-1 provides the basis for the application of this technolo gy in the design of optimal DNA multicomponent anti-T. cruzi vaccines which may ultimately be used for the prevention or treatment of Chagas ' disease.