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OBJECTIVE: The non-obese diabetic (NOD) mouse strain spontaneously develops a disease similar to human Type 1 diabetes (T1D).The aims of our study are to explore the potential mechanisms of an optimized co-expression DNA vaccine containing GAD65 fragment gene and IL-10 gene(SGAD65190-315/IL-10) preventive effect in NOD mice.METHODS: Female NOD mice at 3-4 weeks of age were randomly divided into 2 groups and received intra-muscular injection of either blank vector (n=34) or pBudCE4.1 carrying the SGAD65190-315/IL-10 (n=32).The incidence of diabetes was monitored up to 30 weeks of age.The severity of insulitis, β cells apoptosis rate, and relevant mechanisms were examined.