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Immunization with an engineered mutant trans-sialidase highly protects mice from experimental Trypanosoma cruzi infection: a vaccine candidate.

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.

journal_name

Vaccine

journal_title

Vaccine

authors

Fontanella GH,De Vusser K,Laroy W,Daurelio L,Nocito AL,Revelli S,Contreras R

doi

10.1016/j.vaccine.2008.02.060

subject

Has Abstract

pub_date

2008-05-02 00:00:00

pages

2322-34

issue

19

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(08)00275-2

journal_volume

26

pub_type

杂志文章

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