A plant-based cholera toxin B subunit-insulin fusion protein protects against the development of autoimmune diabetes.
Oral administration of disease-specific autoantigens can prevent or delay the onset of autoimmune disease symptoms. We have generated transgenic potato plants that synthesize human insulin, a major insulin-dependent diabetes mellitus autoantigen, at levels up to 0.05% of total soluble protein. To direct delivery of plant-synthesized insulin to the gut-associated lymphoid tissues, insulin was linked to the C-terminus of the cholera toxin B subunit (CTB). Transgenic potato tubers produced 0.1% of total soluble protein as the pentameric CTB-insulin fusion, which retained GM1-ganglioside binding affinity and native antigenicity of both CTB and insulin. Nonobese diabetic mice fed transformed potato tuber tissues containing microgram amounts of the CTB-insulin fusion protein showed a substantial reduction in pancreatic islet inflammation (insulitis), and a delay in the progression of clinical diabetes. Feeding transgenic potato tissues producing insulin or CTB protein alone did not provide a significant reduction in insulitis or diabetic symptoms. The experimental results indicate that food plants are feasible production and delivery systems for immunotolerization against this T cell-mediated autoimmune disease.
Arakawa
T
T
Center for Molecular Biology and Gene Therapy, Department of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, CA 92350, USA.
Yu
J
J
Chong
D K
DK
Hough
J
J
Engen
P C
PC
Langridge
W H
WH
D000818:Animals; D002772:Cholera Toxin / Q000737:chemistry / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D030821:Plants, Genetically Modified; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics*; D011198:Solanum tuberosum / Q000235:genetics
D007328:Insulin; D011993:Recombinant Fusion Proteins; D002772:Cholera Toxin