The prospect of vaccination to prevent type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease in which genes and environment contribute to cell-mediated immune destruction of insulin-producing beta cells in the pancreatic islets. Primary prevention by traditional 'positive' vaccination awaits evidence that infectious agents trigger T1D. The pre-clinical phase of T1D, in which at-risk individuals can be infected by the presence of autoantibodies to islet antigens, is a window for secondary prevention. The Holy Grail of therapy is 'negative' vaccination to induce immune tolerance against disease-specific autoantigens that drive immune-mediated pathology. This can be achieved by administering autoantigen via a 'tolergenic' (e.g., muscosal, intradermal) route, cell (e.g., resting dendritic cell), mode (e.g., with blockade of c0-stimulation molecules) or form (as an 'altered peptide ligand'). Although effective in rodent models of autoimmune disease, these strategies have so far been disappointing in humans. This review discusses the prospects of vaccination to prevent T1D, focusing on autoantigen-specific mucosal tolerance.