Effects of trans-sialidase enzyme activity, secretion and antigen persistence on the induction of protective immunity against Trypanosoma cruzi infection (VAC8P.1054)

Abstract

Abstract Chagas Disease is a life-threatening illness caused by chronic infection with the Trypanosoma cruzi parasite. It affects up to 11 million people in Latin America, where it is a leading cause of heart disease, making vaccine development critical and worthwhile. Because the T. cruzi trans-sialidase (TS) enzyme is highly conserved and necessary for parasite virulence, it has strong potential as a vaccine target. We have shown that mice can be protected by vaccination with dendritic cells pulsed with a single pair of immunodominant TS epitopes, validating further exploration of TS as a target. We recently have generated live vaccines by transfecting Leishmania major with four TS variations: active secreted, active non-secreted, inactive secreted and inactive non-secreted. These also were transfected into an avirulent, dihydrofolate reductase knock-out strain of Leishmania to investigate the role of antigen persistence versus clearance on immune response. Mice will be infected with the recombinant Leishmania and later challenged with T. cruzi to analyze protective immunity. In preliminary experiments, recombinants were found to express the TS protein and immunizations protected BALB/c mice from infection. This project is the first examining the ability of recombinant Leishmania to serve as vaccine vehicles for Chagas Disease. These experiments will also elucidate the relative importance of inducing central and peripheral memory T cell populations for protective T. cruzi immunity.