Oral administration of a cholera toxin B subunit–insulin fusion protein produced in silkworm protects against autoimmune diabetes

Oral administration of a cholera toxin B subunit–insulin fusion protein produced in silkworm... The oral administration of disease-specific autoantigens can induce oral immune tolerance and prevent or delay the onset of autoimmune disease symptoms. Here, we describe the construction of an edible vaccine consisting of a fusion protein composed of cholera toxin B subunit (CTB) and insulin that is produced in silkworm larvae at levels of up to 0.3 mg/ml of hemolymph. The silkworm bioreactor produced this fusion protein vaccine as the pentameric CTB–insulin form, which retained the GM1-ganglioside binding affinity and the native antigenicity of CTB and insulin. Non-obese diabetic mice fed hemolymph containing microgram quantities of the CTB–insulin fusion protein showed a prominent reduction in pancreatic islet inflammation and a delay in the development of symptoms of clinical diabetes. These results demonstrate that the silkworm bioreactor is a feasible production and delivery system for an oral protein vaccine designed to develop immunological tolerance against T-cell-mediated autoimmune diabetes by regulatory T-cell induction. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Biotechnology Elsevier

Oral administration of a cholera toxin B subunit–insulin fusion protein produced in silkworm protects against autoimmune diabetes

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Publisher
Elsevier
Copyright
Copyright © 2005 Elsevier B.V.
ISSN
0168-1656
eISSN
1873-4863
D.O.I.
10.1016/j.jbiotec.2005.05.027
Publisher site
See Article on Publisher Site

Abstract

The oral administration of disease-specific autoantigens can induce oral immune tolerance and prevent or delay the onset of autoimmune disease symptoms. Here, we describe the construction of an edible vaccine consisting of a fusion protein composed of cholera toxin B subunit (CTB) and insulin that is produced in silkworm larvae at levels of up to 0.3 mg/ml of hemolymph. The silkworm bioreactor produced this fusion protein vaccine as the pentameric CTB–insulin form, which retained the GM1-ganglioside binding affinity and the native antigenicity of CTB and insulin. Non-obese diabetic mice fed hemolymph containing microgram quantities of the CTB–insulin fusion protein showed a prominent reduction in pancreatic islet inflammation and a delay in the development of symptoms of clinical diabetes. These results demonstrate that the silkworm bioreactor is a feasible production and delivery system for an oral protein vaccine designed to develop immunological tolerance against T-cell-mediated autoimmune diabetes by regulatory T-cell induction.

Journal

Journal of BiotechnologyElsevier

Published: Sep 22, 2005

References

  • Nasal administration of CTB–insulin induces active tolerance against autoimmune diabetes in non-obese diabetic (NOD) mice
    Aspord, C.; Thivolet, C.
  • HIV-1 gp120 V3 cholera toxin B subunit fusion gene expression in transgenic potato
    Kim, T.G.; Gruber, A.; Langridge, W.H.
  • Oral administration of insulin to neonates suppresses spontaneous and cyclophosphamide induced diabetes in the NOD mouse
    Maron, R.; Guerau-de-Arellano, M.; Zhang, X.; Weiner, H.L.
  • Coupling of oral human or porcine insulin to the B subunit of cholera toxin (CTB) overcomes critical antigenic differences for prevention of type I diabetes
    Petersen, J.S.; Bregenholt, S.; Apostolopolous, V.; Homann, D.; Wolfe, T.; Hughes, A.; De Jongh, K.; Wang, M.; Dyberg, T.; Von Herrath, M.G.
  • Genetic fusion of human insulin B-chain to the B-subunit of cholera toxin enhances in vitro antigen presentation and induction of bystander suppression in vivo
    Sadeghi, H.; Bregenholt, S.; Wegmann, D.; Petersen, J.S.; Holmgren, J.; Lebens, M.
  • Immune therapy for autoimmune diseases
    Steinman, L.

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