Journal of Clinical and Cellular Immunology
Open Access

Abstract

Reverse Vaccination and Treatment of Type 1 Diabetes Using Plant-Produced Autoantigens and Anti-inflammatory Cytokines

M Lucrecia Alvarez, Stefania Cotta Done and Guy A Cardineau

Type 1 diabetes (T1D) is an autoimmune form of diabetes mellitus that accounts for about 10% of all diabetes cases and occurs predominantly during childhood or adolescence. The disease initiates when most of the insulinproducing β-cells in the pancreas are destroyed by autoimmune cells, including T-helper 1 cells, cytotoxic lymphocytes and dendritic cells. The major autoantigens in T1D are insulin, glutamic acid decarboxylase, and insulinoma antigen. At-risk individuals with underlying islet inflammation can be identified by the presence of circulating autoantibodies to these specific islet antigens many years before the clinical onset of T1D, thus, providing a window for prevention strategies. Currently, there is no definitive cure for T1D; therefore, more effective therapeutic interventions for prevention of diabetes onset and progression are urgently needed. Vaccination with autoantigens to promote selfantigen- specific tolerance represents the most specific and safest means of preventing autoimmune diseases. Autoantigens administered by the mucosal route, which is “tolerogenic” by nature, is the most effective way to prevent or treat autoimmune diseases. However, the two major drawbacks of oral vaccination with autoantigens are the large quantities required to induce significant tolerance, presumably because the protein is partially degraded in the stomach, and the high cost of producing recombinant autoantigens using the conventional cell culture-based platforms. The expression of autoantigens in plants and the oral delivery of the plant tissue expressing the target antigen offer a potential solution for these two drawbacks. The goal of this review is to outline novel diabetes vaccine strategies based on β-cell autoantigens with a focus on the advantages and potential of plant-produced islets self antigens and anti-inflammatory cytokines for the prevention and treatment of T1D.