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

Abstract
Granulomatous inflammation in schistosomiasis is a delayed-type hypersensitivity reaction mediated by CD4+ T cells specific for parasite egg antigens (Ags). In an attempt to control T-cell responses leading to excessive harmful 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 protein with demonstrated capacity to suppress inflammatory T-cell functions after mucosal administration. Treatment with CTB-SEA significantly conjugate a reduced liver granuloma formation in infected mice associated with decreased SEA specific Th1- and Th2-type immune responses by liver leukocytes. Importantly, treatment with CTB-SEA conjugate also significantly reduced the mortality in chronically infected mice. In S. mansoni-infected large-granuloma forming CBA mice, i.n. treatment with purified Sm-p40, the major egg antigen, conjugated to CTB likewise significantly inhibited hepatic egg granuloma formation. A reduction of SEA-driven lymphoproliferation and of interferon (IFN)-gamma, interleukin (IL)-4 and IL-5 production, together with an increase in transforming growth factor (TGF)-beta1 production, were observed 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-p40 antigen in conjunction with CTB is highly effective in curtailing immunopathologic manifestations of schistosomiasis in vivo in infected hosts.
AuthorsJ B Sun, M J Stadecker, N Mielcarek, M Lakew, B L Li, H J Hernandez, C Czerkinsky, J Holmgren
JournalScandinavian journal of immunology (Scand J Immunol) Vol. 54 Issue 5 Pg. 440-7 (Nov 2001) ISSN: 0300-9475 [Print] England
PMID11696194 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, Helminth
  • Helminth Proteins
  • Vaccines, Conjugate
  • p40 egg antigen, Schistosoma
  • Cholera Toxin
Topics
  • Administration, Intranasal
  • Animals
  • Antigens, Helminth (administration & dosage)
  • Cholera Toxin (administration & dosage)
  • Female
  • Granuloma (immunology, pathology, prevention & control)
  • Helminth Proteins
  • Immunity, Mucosal
  • Liver (immunology, pathology)
  • Liver Diseases (immunology, pathology, prevention & control)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Ovum (immunology)
  • Schistosoma mansoni (immunology)
  • Schistosomiasis mansoni (immunology, pathology, therapy)
  • Th1 Cells (immunology)
  • Th2 Cells (immunology)
  • Vaccines, Conjugate (administration & dosage)

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