Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases.
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.
Zoology Department, Faculty of Science, Cairo University Cairo, Egypt.
Rashika
R
El Ridi
Zoology Department, Faculty of Science, Cairo University Cairo, Egypt.
Hatem
H
Tallima
Medical Biology Centre, School of Biological Sciences, Queen's University Belfast Belfast, Northern Ireland.
John P
JP
Dalton
The i-three Institute, University of Technology at Sydney Ultimo, Sydney, NSW, Australia.
Sheila
S
Donnelly
Th2 immune response; cathepsin B; cysteine peptidase; papain; schistosome