Immunization with DNA encoding an immunodominant peptide of insulin prevents diabetes in NOD mice.
DNA vaccination is an effective means of protecting experimental animals against infectious pathogens and cancer and has more recently been used to prevent autoimmune disease. Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease characterized by T-cell-mediated destruction of the insulin-secreting beta cells in the pancreas. The NOD mouse is an animal model of IDDM in which several autoantigens, including insulin, have been identified. In this study we demonstrate that vaccination of NOD mice with DNA encoding an immunodominant peptide of insulin (residues 9-23 of the B chain) protects the animals from developing diabetes. Animals injected intramuscularly with a bacterial plasmid encoding the insulin B chain peptide show significantly lower disease incidence and delayed onset of disease when compared to controls. Protection appears to be mediated by insulin B (9-23)-specific down-regulation of IFN-gamma. Our results confirm that DNA vaccination has a protective effect on autoimmunity, the understanding of which will reveal new insights into the immune system and open doors for novel therapies.
Urbanek-Ruiz
I
I
Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California 94305, USA.
Ruiz
P J
PJ
Paragas
V
V
Garren
H
H
Steinman
L
L
Fathman
C G
CG
D000818:Animals; D015551:Autoimmunity; D004247:DNA / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D007114:Immunization; D016056:Immunodominant Epitopes; D007328:Insulin / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D010455:Peptides / Q000276:immunology; D051381:Rats
D016056:Immunodominant Epitopes; D007328:Insulin; D010455:Peptides; D004247:DNA