Vaccination with Trypomastigote Surface Antigen 1-Encoding Plasmid DNA Confers Protection against Lethal Trypanosoma cruzi Infection

Abstract

ABSTRACT DNA vaccination was evaluated with the experimental murine model of Trypanosoma 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) class I-restricted CD8 + cytotoxic T-lymphocyte (CTL) responses, was used as the model antigen. Following the intramuscular immunization of H-2 b and H-2 d mice with a plasmid DNA encoding an N-terminally truncated TSA-1 lacking or containing the C-terminal nonapeptide tandem repeats, the antibody level, CTL response, and protection against challenge with T. cruzi were assessed. In H-2 b mice, antiparasite antibodies 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 protective H-2K b -restricted TSA-1 515–522 epitope. In H-2 d mice, inoculation with either of the two TSA-1-expressing vectors effectively generated antiparasite antibodies and primed CTLs that lysed T. cruzi -infected cells in an antigen-specific, MHC class I-restricted, and CD8 + -T-cell-dependent manner. When TSA-1 DNA-vaccinated animals were challenged 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 expressing TSA-1 provides the basis for the application of this technology in the design of optimal DNA multicomponent anti- T. cruzi vaccines which may ultimately be used for the prevention or treatment of Chagas’ disease.