Oral administration of a cholera toxin B subunit-insulin fusion protein produced in silkworm protects against autoimmune diabetes.
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.
Gong
Zhaohui
Z
Institute of Biochemistry, College of Life Sciences, Zhejiang University, 268 Kaixuan Road, Hangzhou 310029, China.
Jin
Yongfeng
Y
Zhang
Yaozhou
Y
D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation; D001483:Base Sequence; D012831:Bombyx / Q000235:genetics; D002772:Cholera Toxin / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005260:Female; D005677:G(M1) Ganglioside / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D015202:Protein Engineering / Q000379:methods; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D022462:Vaccines, Edible / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
D007328:Insulin; D011993:Recombinant Fusion Proteins; D022462:Vaccines, Edible; D005677:G(M1) Ganglioside; D002772:Cholera Toxin