Abstract
Oral tolerance has been applied successfully as a potential therapeutic strategy for preventing and treating autoimmune diseases including type 1 diabetes. In this paper we constructed an edible vaccine consisting of a fusion protein composed of cholera toxin B subunit (CTB) and insulin B chain (InsB) that was produced in silkworm larvae. The silkworm larvae produced this fusion protein at levels of up to 0.97 mg/ml of hemolymph as the pentameric CTB–InsB form, which retained the GM1-ganglioside binding affinity and the native antigenicity of CTB. Non-obese diabetic mice fed hemolymph containing microgram quantities of the CTB–InsB fusion protein showed a prominent reduction in pancreatic islet inflammation and a delay in the development of diabetic symptoms. This study demonstrates that silkworm-produced CTB–InsB fusion protein can be used as an ideal oral protein vaccine for induction of immunological tolerance against autoimmune diabetes.
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