Vaccines for type 1 diabetes

Abstract

By primary prevention aimed at avoiding or averting environmental factors thought to promote disease in genetically at-risk individuals T1D would be eradicated ideally, but these factors have not been identified and may be ubiquitous. Since the early 1980s, secondary prevention, after the disease process has started, has been the focus of considerable attention and with many candidate agents, mainly immunosuppressive drugs have been trialled, usually after the onset of clinical diabetes. Prevention is however more applicable to early, preclinical disease rather than to recent onset clinical disease, when beta cell destruction is more advanced. Prevention of the infectious disease by exposing the immune system to the weakened or dead infectious agent has been a traditional vaccination method. Alternate method called “inverse vaccination” (the inhibition of immune response) arrests autoimmunity through manipulation of the innate and adaptive arms of the immune system. Inverse vaccination specifically reduces a pathological adaptive autoimmune response. Targeted reduction of unwanted antibody and T-cell responses to autoantigens is allowed by inverse vaccination, while leaving the remainder of the immune system intact. Varying degree of success in suppression of β-cell autoimmunity in NOD mice have been shown by current options for treatment of autoimmunity such as immunosuppressive drugs (e.g. cyclosporine) and anti T-cell antibodies (e.g. anti-CD3 antibodies). But the drawback with these methods is that it requires repeated administration and may lead to non-specific harmful effects such as interference with normal immune system functions. Whereas, antigen specific immunotherapy (ASI) uses inverse vaccination for a specific auto-antigen. The advantage with the ASI is selective inactivation of auto-reactive T cells without interference in normal immune function. Major examples of antigen specific immunotherapy agent at various stage of clinical trials are alum formulated glutamic acid decarboxylase and heat shock protein and peptide 277.