Plasmid vaccination with insulin B chain prevents autoimmune diabetes in nonobese diabetic mice

The insulin B (InsB) chain bears major type I diabetes-associated epitopes of significance for disease in humans and nonobese diabetic (NOD) mice. Som atic expression of InsB chain initiated early in life by plasmid inoculatio n resulted in substantial protection of female NOD mice against disease. Th is was associated with a T2 shift in spleen, expansion of IL-4-producing an d, to a lesser extent, of IFN-gamma -secreting T cells in pancreatic lymph nodes, as well as intermolecular Th2 epitope spreading to glutamic acid dec arboxylase determinants. A critical role of IL-4 for the Ag-specific protec tive effect triggered by plasmid administration was revealed in female IL-4 (-/-) NOD mice that developed diabetes and higher Th I responses. Coadminis tration of IL-4-expressing plasmid or extension of the vaccination schedule corrected the unfavorable response of male NOD mice to DNA vaccination wit h InsB chain. Thus, plasmid-mediated expression of the InsB chain early in diabetes-prone mice has the potential to prevent transition to full-blown d isease depending on the presence of IL-4.