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lüll Autoantigen based vaccines for type 1 diabetes Nicholas D; Odumosu O; Langridge WHDiscov Med 2011[Apr]; 11 (59): 293-301Type 1 diabetes is an organ-specific autoimmune disease caused by chronic inflammation (insulitis), which damages the insulin producing beta-cells of the pancreatic Islets of Langerhans. Dendritic cells (DCs) are generally the first cells of the immune system to process beta-cell autoantigens and, by promoting autoreactivity, play a major role in the onset of insulitis. Although no cure for diabetes presently exists, the onset of insulitis can be diminished in the non-obese diabetic (NOD) mouse type 1 diabetes model by inoculation with endogenous beta-cell autoantigens. These include the single peptide vaccines insulin, GAD(65) (glutamic acid decarboxylase), and DiaPep277 (an immunogenic peptide from the 60-kDa heat shock protein). DiaPep277 is the only autoantigen so far to demonstrate positive results in human clinical trials. Diamyd (an alum adjuvant + recombinant GAD(65) protein formulation) has shown great promise for suppressing beta-cell autoreactivity in phase I and II clinical trials. While Diamyd preserved residual insulin secretion in early-onset type 1 diabetes patients, it did not reduce the amounts of insulin required to maintain euglycemia. Recently, multi-component vaccines composed of the anti-inflammatory cytokine (IL-10) and insulin or GAD(55) linked to an immunostimulatory molecule, the cholera toxin B subunit, were shown to safely and completely inhibit diabetes onset in NOD mice. This result suggests that multi-component vaccine strategies are promising for prevention and reversal of diabetes autoimmunity in humans. Here we focus on the development of autoantigen vaccines for type 1 diabetes and demonstrate that multi-component vaccines are promising candidates for type 1 diabetes clinical studies.|Animals[MESH]|Autoantigens/*immunology[MESH]|Dendritic Cells/immunology[MESH]|Diabetes Mellitus, Type 1/*immunology/pathology/*prevention & control[MESH]|Humans[MESH]|Immunotherapy[MESH]|Peptides/immunology/therapeutic use[MESH]|Vaccines/*immunology[MESH] |