title: Autoantigen based vaccines for type 1 diabetes.
abstract: Type 1 diabetes is an organ-specific autoimmune disease caused by chronic inflammation (insulitis), which damages the insulin producing β-cells of the pancreatic Islets of Langerhans. Dendritic cells (DCs) are generally the first cells of the immune system to process β-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 β-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 β-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.
authors.affiliation: Center for Health Disparities and Molecular Medicine, Department of Biochemistry, Loma Linda University School of Medicine, California 92354, USA.
authors.forename: Dequina
authors.initials: D
authors.lastname: Nicholas
authors.forename: Oludare
authors.initials: O
authors.lastname: Odumosu
authors.forename: William H R
authors.initials: WH
authors.lastname: Langridge
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007167:Immunotherapy; D010455:Peptides / Q000276:immunology / Q000627:therapeutic use; D014612:Vaccines / Q000276:immunology*
chemical_list: D001324:Autoantigens; D010455:Peptides; D014612:Vaccines