Immunization with a novel engineered mutant trans-sialidase protects mice from experimental Trypanosoma cruzi infection. A vaccine candidate.

FONTANELLA, G.H.- DE VUSEER, K.; LAROY, W.; DAURELIO, L.D.; NOCITO, A.; CONTRERAS, R.; REVELLI, S.S.

Río de Janeiro, Brasil.

Congreso; 13th International Congress of Immunology.; 2007

Brazilian Society of Immunology-SBI and the Latin American Society of immunology

Chagas’ disease is a major tropical disease for which a cure for chronic phase does not exist yet. T. cruzi trans-sialidase (TS) seems to be involved in relevant processes such as infectivity, host survival and, very importantly, disease pathogenesis. In this study we show that mice vaccinated with an engineered enzymatically deficient mutant TS containing the catalytic domain without the immunodominant SAPA repeats, were protected against T. cruzi infection. Adult male BALB/c mice were immunized with mutant protein, purified from Pichia pastoris yeast, using three inoculations in Freund’s adjuvant (subcutaneous route). All immunized mice were protected against challenge with a lethal dose of T. cruzi trypomastigotes (14 days after the last immunization, Tulahuén strain). During acute phase of infection, parasitemia was notable higher in non-immunized groups than in vaccinated mice (median values in these animals were always zero), p<0.001. Furthermore, the protected immunized mice developed no clinical or tissue evidence of infection throughout the study. In contrast, a 60-90% mortality and 100% occurrence of myocardial lesions were observed in the non-immunized counterparts (60 days post-infection). Titers of circulating antibody against TS did not correlate with protection, while anti-SAPA antibodies were coincident with disease severity. Further studies indicated that a single inoculation of mutant recombinant protein in Freund’s complete adjuvant was not associated with blood or organic alterations, per se. Mutant TS vaccination seems to be a promising tool for immune intervention strategies in Chagas’ disease, aimed at preventing T. cruzi-related heart tissue damage.