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Immunization with an engineered mutant trans-sialidase highly protects mice from experimental Trypanosoma cruzi
Germán H Fontanella1, Kristof De Vusser, Wouter Laroy
1Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Argentina.
Abstract:
Chagas' disease is a major tropical disease for which a cure for chronic phase does not exist yet. Trypanosoma 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 (Shed Acute Phase Antigen) repeats, were highly 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. All immunized mice were protected against challenge with a lethal dose of T. cruzi trypomastigotes. The protected immunized mice developed no clinical or tissue evidence of infection throughout the study. In contrast, 60-90% mortality and 100% occurrence of myocardial lesions were observed in the non-immunized counterparts. 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.
Insights
Vaccinating mice with a modified Trypanosoma cruzi trans-sialidase (TS) protein protected them from infection. This engineered TS mutant shows promise for preventing Chagas
Area of Science:
- Immunology
- Parasitology
- Tropical Diseases
Background:
- Chagas' disease, caused by *Trypanosoma cruzi*, lacks a cure for its chronic phase.
- The *Trypanosoma cruzi* trans-sialidase (TS) enzyme is implicated in infection, host survival, and disease pathogenesis.
Purpose of the Study:
- To evaluate the protective efficacy of an engineered, enzymatically deficient mutant TS against *T. cruzi* infection.
- To assess the role of anti-TS and anti-SAPA antibodies in protection and disease severity.
Main Methods:
- Adult male BALB/c mice were immunized with a purified, catalytically inactive mutant TS lacking SAPA repeats.
- Immunization involved three inoculations with the mutant protein in Freund's adjuvant.
- Protected and non-immunized mice were challenged with a lethal dose of *T. cruzi* trypomastigotes.
Main Results:
- All immunized mice were fully protected against lethal *T. cruzi* challenge, showing no clinical or tissue evidence of infection.
- Non-immunized control mice exhibited 60-90% mortality and 100% myocardial lesions.
- Antibody titers against TS did not correlate with protection, whereas anti-SAPA antibodies correlated with disease severity.
Conclusions:
- Vaccination with the engineered mutant TS provides high protection against *T. cruzi* infection in mice.
- This mutant TS vaccination strategy is a promising approach for immune intervention against Chagas' disease.
- The findings suggest potential for preventing *T. cruzi*-induced cardiac tissue damage.
