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Each year schistosomiasis afflicts up to 600 million people in 74 tropical and sub-tropical countries, predominantly in the developing world. Yet we depend on a single drug, praziquantel, for its treatment and control. There is no vaccine available but one is urgently needed especially since praziquantel-resistant parasites are likely to emerge at some time in the future. The disease is caused by several worm species of the genus  Schistosoma . These express several classes of papain-like cysteine peptidases, cathepsins B and L, in various tissues but particularly in their gastrodermis where they employ them as digestive enzymes. We have shown that sub-cutaneous injection of recombinant and functionally active  Schistosoma mansoni  cathepsin B1 (SmCB1), or a cathepsin L from a related parasite  Fasciola hepatica  (FhCL1), elicits highly significant protection (up to 73%) against an experimental challenge worm infection in murine models of schistosomiasis. The immune modulating properties of this subcutaneous injection can boost protection levels (up to 83%) when combined with other  S. mansoni  vaccine candidates, glyceraldehyde 3-phosphate dehydrogenase (SG3PDH) and peroxiredoxin (PRX-MAP). Here, we discuss these data in the context of the parasite’s biology and development, and provide putative mechanism by which the native-like cysteine peptidase induce protective immune responses.

Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases