Cysteine peptidases as schistosomiasis vaccines with inbuilt adjuvanticity.
Schistosomiasis is caused by several worm species of the genus Schistosoma and afflicts up to 600 million people in 74 tropical and sub-tropical countries in the developing world. Present disease control depends on treatment with the only available drug praziquantel. No vaccine exists despite the intense search for molecular candidates and adjuvant formulations over the last three decades. Cysteine peptidases such as papain and Der p 1 are well known environmental allergens that sensitize the immune system driving potent Th2-responses. Recently, we showed that the administration of active papain to mice induced significant protection (P<0.02, 50%) against an experimental challenge infection with Schistosoma mansoni. Since schistosomes express and secrete papain-like cysteine peptidases we reasoned that these could be employed as vaccines with inbuilt adjuvanticity to protect against these parasites. Here we demonstrate that sub-cutaneous injection of functionally active S. mansoni cathepsin B1 (SmCB1), or a cathepsin L from a related parasite Fasciola hepatica (FhCL1), elicits highly significant (P<0.0001) protection (up to 73%) against an experimental challenge worm infection. Protection and reduction in worm egg burden were further increased (up to 83%) when the cysteine peptidases were combined with other S. mansoni vaccine candidates, glyceraldehyde 3-phosphate dehydrogenase (SG3PDH) and peroxiredoxin (PRX-MAP), without the need to add chemical adjuvants. These studies demonstrate the capacity of helminth cysteine peptidases to behave simultaneously as immunogens and adjuvants, and offer an innovative approach towards developing schistosomiasis vaccines.
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
National Liver Institute, Menoufiya University, Shebin El-Kom, Menoufiya, Egypt.
Sahar
S
Selim
The i-three Institute, University of Technology Sydney (UTS), Ultimo, Sydney, Australia.
Sheila
S
Donnelly
Institute of Parasitology, McGill University, Sainte Anne de Bellevue, Canada.
Sophie
S
Cotton
Institute of Parasitology, McGill University, Sainte Anne de Bellevue, Canada.
Bibiana
B
Gonzales Santana
Institute of Parasitology, McGill University, Sainte Anne de Bellevue, Canada ; School of Biological Sciences, Queen's University Belfast, Belfast, Northern Ireland.
John P
JP
Dalton
D000276:Adjuvants, Immunologic; D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D000947:Antigens, Helminth / Q000737:chemistry / Q000276:immunology*; D002401:Cathepsin B / Q000737:chemistry / Q000276:immunology*; D002403:Cathepsins / Q000737:chemistry / Q000276:immunology*; D005210:Fasciola hepatica / Q000737:chemistry / Q000201:enzymology; D005260:Female; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / Q000737:chemistry / Q000276:immunology; D007110:Immunity, Active / Q000187:drug effects; D051379:Mice; D054464:Peroxiredoxins / Q000737:chemistry / Q000276:immunology; D010843:Pichia / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D012550:Schistosoma mansoni / Q000737:chemistry / Q000201:enzymology / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D054464:Peroxiredoxins; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+); D002403:Cathepsins; D002401:Cathepsin B; C028217:cathepsin S