Immunization with DNA encoding an immunodominant peptide of insulin prevents diabetes in NOD mice

DNA vaccination is an effective means of protecting experimental animals ag ainst infectious pathogens and cancer and has more recently been used to pr event autoimmune disease. Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease characterized by T-cell-mediated destruction of the insu lin-secreting beta cells in the pancreas. The NOD mouse is an animal model of IDDM in which several autoantigens, including insulin, have been identif ied. In this study we demonstrate that vaccination of NOD mice with DNA enc oding an immunodominant peptide of insulin (residues 9-23 of the B chain) p rotects the animals from developing diabetes. Animals injected intramus-cul arly with a bacterial plasmid encoding the insulin B chain peptide show sig nificantly lower disease incidence and delayed onset of disease when compar ed to controls. Protection appears to be mediated by insulin B (9-23)-speci fic down-regulation of IFN-gamma. Our results confirm that DNA vaccination has a protective effect on autoimmunity, the understanding of which will re veal new insights into the immune system and open doors for novel therapies . (C) 2001 Academic Press.