Shen Lili, Lu Shiping, Huang Dongcheng, Li Guoliang, Liu Kunfeng, Cao Rongyue, Zong Li, Jin Liang, Wu Jie
1 Minigene Pharmacy Laboratory, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
2 Institute of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Diab Vasc Dis Res. 2017 May;14(3):184-190. doi: 10.1177/1479164116664189. Epub 2017 Mar 1.
Recent studies have investigated the potential of type 1 diabetes mellitus-related autoantigens, such as heat shock protein 60, to induce immunological tolerance or to suppress the immune response. A functional 24-residue peptide derived from heat shock protein 60 (P277) has shown anti-type 1 diabetes mellitus potential in experimental animals and in clinical studies, but it also carries a potential atherogenic effect. In this study, we have modified P277 to retain an anti-type 1 diabetes mellitus effect and minimize the atherogenic potential by replacing the P277 B epitope with another diabetes-associated autoantigen, insulinoma antigen-2 (IA-2), to create the fusion peptide IA-2-P2. In streptozotocin-induced diabetic C57BL/6J mice, the IA-2-P2 peptide displayed similar anti-diabetic effects to the control P277 peptide. Also, the IA-2-P2 peptide did not show atherogenic activity in a rabbit model. Our findings indicate the potential of IA-2-P2 as a promising vaccine against type 1 diabetes mellitus.
最近的研究探讨了1型糖尿病相关自身抗原（如热休克蛋白60）诱导免疫耐受或抑制免疫反应的潜力。一种源自热休克蛋白60的功能性24个氨基酸残基的肽（P277）在实验动物和临床研究中已显示出抗1型糖尿病的潜力，但它也具有潜在的致动脉粥样硬化作用。在本研究中，我们对P277进行了修饰，通过用另一种糖尿病相关自身抗原胰岛瘤抗原-2（IA-2）替代P277的B表位，以保留抗1型糖尿病的作用并将致动脉粥样硬化潜力降至最低，从而创建了融合肽IA-2-P2。在链脲佐菌素诱导的糖尿病C57BL/6J小鼠中，IA-2-P2肽表现出与对照P277肽相似的抗糖尿病作用。此外，IA-2-P2肽在兔模型中未显示出致动脉粥样硬化活性。我们的研究结果表明，IA-2-P2作为一种有前景的抗1型糖尿病疫苗具有潜力。
