Suppression of diabetes in non-obese diabetic (NOD) mice by oral administration of a cholera toxin B subunit-insulin B chain fusion protein vaccine produced in silkworm.
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 0.97mg/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.
Gong
Zhaohui
Z
School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo 315211, China.
Jin
Yongfeng
Y
Zhang
Yaozhou
Y
D000284:Administration, Oral; D000818:Animals; D012831:Bombyx; D002772:Cholera Toxin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy*; D005260:Female; D007108:Immune Tolerance; D007328:Insulin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D007328:Insulin; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D002772:Cholera Toxin