Inverse vaccination with islet autoantigens to halt progression of autoimmune diabetes

Abstract

The incidence of autoimmune diabetes mellitus is growing worldwide; currently the only treatment is injection of insulin formulations to maintain glycemic control. Islet transplantation has been examined as a potential cure for diabetes. However, it has several limitations, including side effects of immunosuppressive agents required to prevent graft rejection. Other approaches have been to examine immune modulation to halt or prevent the autoimmune attack, with the hope that by preventing tissue damage, it will eventually regenerate and permit patients to be free from insulin injections. The focus of the current review is the three major antigen-based vaccines, insulin, glutamic acid decarboxylase 65 (GAD65; Diamyd), and heat shock protein 60 (Hsp60; DiaPep277), with respect to their mechanism of action, preclinical results, and published results from clinical trials. Despite promising results with these three antigens in mice and humans, efficacy has been limited in clinical trials. Drug Dev Res 72: 788-804, 2011. r