Vaccination with calpain induces a Th1-biased protective immune response against Schistosoma japonicum

A large subunit of calpain, a calcium-activated neutral proteinase, from Sc histosoma japonicum was cloned and expressed in Escherichia coli. When BALB /c mice were immunized with purified recombinant calpain (r-calpain) emulsi fied in complete Freund's adjuvant, a significant reduction in the number o f recovered worms and also in egg production per female worm was observed ( P < 0.01). Spleen cells of the immunized mice showed enhanced production of gamma interferon (IFN-<gamma>) by activated CD4(+) T cells. Considering ou r observation of elevated expression of inducible nitric oxide synthase mRN A in immunized mice, r-calpain-induced IFN-gamma seemed to upregulate the p roduction of nitric oxide by macrophages and subsequently mediated the kill ing of schistosomulae in the lung. On the other hand, spleen cells of immun ized mice showed only faint interleukin-4 production in response to r-calpa in in vitro, suggesting that immunization with r-calpain alters the Th1-Th2 balance in murine hosts even during a Th2-promoting S. japonicum infection . Furthermore, histopathological study of the livers of immunized mice show ed that granulomas formed around eggs were diminished in both size and numb er. Egg production by female worms was clearly decreased in immunized mice, suggesting that r-calpain also has antifecundity effects. Taken together, these results point to S. japonicum calpain as a potential vaccine candidat e for both worm killing and disease prevention, possibly through the induct ion of a strong Th1-dominant environment in immunized mice.