Intramuscular injection of plasmid DNA encoding intracellular or secreted glutamic acid decarboxylase causes decreased insulitis in the non- obese diabetic mouse

O u r g o a l i s t o determine whether gene vaccination can be used for the treatment of insulindependent diabetes mell i tus (IDDM), an autoimmune disease. In this work, weanling non-obese diabetic (NOD) mice, an animal model system for the study of IDDM, received intramuscular injections of “naked” plasmid DNA encoding either intracellular or secreted human glutamic acid decarboxylase (GAD), one of the major autoantigens recognized during the onset of IDDM. Seven weeks later, each pancreas was scored for insulitis, an inflammation indicative of the disease. Mice treated with either type of gad gene-carrying plasmid showed a significant decrease in the severity of insulitis when compared to controls. These results suggest that vaccination using autoantigenencoding genes may provide a means of treating IDDM.