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. [ABSTRACT FROM AUTHOR]