Nasal administration of Schistosoma mansoni egg antigen-cholera B subunit conjugate suppresses hepatic granuloma formation and reduces mortality in S-mansoni-infected mice

Granulomatous inflammation in schistosomiasis is a delayed-type hypersensit ivity reaction mediated by CD4(+) T cells specific for parasite egg antigen s (Ags). In an attempt to control T-cell responses leading to excessive har mful inflammation and granuloma formation, especially in the liver, BALB/c mice were intranasally (i.n.) treated with soluble Schistosoma mansoni egg Ags (SEA) conjugated to cholera toxin B subunit (CTB), a mucosa-binding pro tein with demonstrated capacity to suppress inflammatory T-cell functions a fter mucosal administration. Treatment with CTB-SEA significantly conjugate a reduced liver granuloma formation in infected mice associated with decre ased SEA specific Th1- and Th2-type immune responses by liver leukocytes. I mportantly, treatment with CTB-SEA conjugate also significantly reduced the mortality in chronically infected mice. In S. mansoni-infected large-granu loma forming CBA mice, i.n. treatment with purified Sm-p40, the major egg a ntigen, conjugated to CTB likewise significantly inhibited hepatic egg gran uloma formation. A reduction of SEA-driven lymphoproliferation and of inter feron (IFN)-gamma, interleukin (IL)-4 and IL-5 production, together with an increase in transforming growth factor (TGF)-beta (1) production, were obs erved in splenic cells from CTB-Sm-p40-treated SEA-sensitized mice, as well as in liver leukocytes from CTB-Sm-p40-treated schistosome-infected mice. These results indicate that mucosal administration of SEA or purified Sm-p4 0 antigen in conjunction with CTB is highly effective in curtailing immunop athologic manifestations of schistosomiasis in vivo in infected hosts.