Immunotherapy of autoimmune diabetes by nasal administration of tandem glutamic acid decarboxylase 65 peptides.
Mucosally induced tolerance is an attractive strategy for immunotherapy of autoimmune diseases. Treatment of nonobese diabetic (NOD) mice with a mixture of autoantigen peptides is better geared toward slowing the progression of late stage type 1 diabetes (T1D) than treatment with any of the peptides alone. In this study, we constructed a fusion protein CTB-GADIII. It contains cholera toxin B subunit (CTB) and three tandem peptides derived from glutamic acid decarboxylase 65 (GAD65), p217-236, p524-538 and p290-306. The purified renatured pentamer fusion protein was effective in inhibiting the development of diabetes in NOD mice when the mice were nasally immunized three times (8w, 10w and 12w). Prevention of diabetes was associated with special humoral immune tolerance against tandem peptides GADIII. These data indicate that using CTB as a vaccine carrier, tandem GAD65 peptides can prevent T1D in NOD mice at the late stage of disease.
Laboratory of Minigene Pharmacy, School of Life Science and Technology, China Pharmaceutical University, Tongjia Xiang, Nanjing 210009, PR China. wanghuaqian2006@hotmail.com
Huaqian
H
Wang
Jie
J
Yang
Liang
L
Jin
Jiao
J
Feng
Yong
Y
Lu
Yunxiao
Y
Sun
Taiming
T
Li
Rongyue
R
Cao
Jie
J
Wu
Hao
H
Fan
Jingjing
J
Liu
D000281:Administration, Intranasal; D000818:Animals; D002772:Cholera Toxin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D018450:Disease Progression; D005260:Female; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007108:Immune Tolerance; D056724:Immunity, Humoral; D007114:Immunization; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D002772:Cholera Toxin; C439756:GAD65 (217-236); D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2