The Prospect of Vaccination to Prevent Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) is an autoimmune disease in which genes and environment contribute to cell-mediated immune destruction of insulin-producing ? cells in the islets of the pancreas. An understanding of pathogenetic mechanisms paves the way for vaccination strategies to prevent T1D. Primary prevention by traditional ‘positive’ vaccination awaits clear evidence of a the role for infectious agents in triggering the disease process. Following initiation of disease, at-risk individuals with underlying islet inflammation can be identified by the presence of circulating autoantibodies to islet antigens. This pre-clinical phase of T1D, before insulin deficiency leads to symptoms of hyperglycemia, provides a window for secondary prevention. The therapeutic Holy Grail in autoimmune disease is ‘negative’ vaccination against autoantigens that drive immune-mediated pathology, to induce disease-specific immune tolerance. This can be achieved by administering autoantigen via a ‘tolerogenic’ (e.g. mucosal) route, cell (e.g. resting dendritic cell), mode (e.g. with blockade of co-stimulation molecules) or form (as an ‘altered peptide ligand’). These strategies to induce immune tolerance are effective in rodent models of autoimmune disease, but in application to humans the results have so far been disappointing. This review discusses the prospects of vaccination to prevent T1D, focusing on autoantigen-specific mucosal tolerance.