Immunization with an engineered mutanttrans-sialidase highly protects mice from experimentalTrypanosoma cruziinfection: A vaccine candidate

• Published in: Vaccine 2008-05, Vol.26 (19), p.2322
• Main Authors: Fontanella, Germán H, De Vusser, Kristof, Laroy, Wouter, Daurelio, Lucas, Nocito, Ana Lía, Revelli, Silvia, Contreras, Roland
• Format: Article
• Language: English
• Subjects: Immune system; Immunization; Parasites; Protozoa; Vaccines; Vector-borne diseases
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.02.060

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 againstT. cruziinfection. Adult male BALB/c mice were immunized with mutant protein, purified fromPichia pastorisyeast, using three inoculations in Freund's adjuvant. All immunized mice were protected against challenge with a lethal dose ofT. cruzitrypomastigotes. 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 preventingT. cruzi-related heart tissue damage.