A novel multi-epitope vaccine based on Dipeptidyl Peptidase 4 prevents streptozotocin-induced diabetes by producing anti-DPP4 antibody and immunomodulatory effect in C57BL/6J mice

作者：Li, Zhixin; Fang, Jinzhi; Jiao, Rui; Wei, Xiaomin; Ma, Yanjie; Liu, Xiaoran; Cheng, Peng; Li, Taiming^*

来源：Biomedicine & Pharmacotherapy, 2017, 89: 1467-1475.

DOI：10.1016/j.biopha.2017.01.089

• Diabetes
• Dipeptidyl peptidase 4
• Autoantigens
• Antibody
• beta-cell

Type 1 diabetes is a chronic organ-specific autoimmune disease in which selective destruction of insulin-producing beta-cells leads to impaired glucose metabolism and its attendant complications. A series of Dipeptidyl peptidase 4 (DPP4) inhibitors have been developed and granted approval in the treatment of type 2 diabetes mellitus by inhibiting the enzymatic degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). An increasing number of studies have shown the potential benefits of DPP4 inhibitors for type 1 diabetes. In this report, we describe a novel multi-epitope vaccine comprising a B cell epitope of DPP4, an anti-diabetic B cell epitope of Insulinoma antigen-2 (IA-2) and a Th2 epitope of P277 peptide in human heat shock protein 60 (HSP60). Immunization with the multi-epitope vaccine in streptozotocin (STZ) treated mice successfully induced specific anti-DPP4 antibody and increased serum GLP-1 level. Moreover, this antibody lasted for more than 7 weeks. Inoculation of this vaccine in C57BL/6J mice significantly reduced blood glucose level, improved glucose excursion and increased plasma insulin concentration. Consistent with a lower diabetic and insulitis incidence, induced splenic T cell proliferation and tolerance were observed. IFN-gamma and IL-2 secretion reduced, but IL-10 and IL-4 increased significantly in the Dipeptidyl Peptidase 41-Insulinoma antigen-2 (5)-P2-1 (D41-IP) treated mice compared to the Insulinoma antigen-2(5)-P2-1 (IA2(5) P2-1) and control group due to the potential immunomodulatory effect of the epitopes in the vaccine. Our results demonstrate that this multi-epitope vaccine may serve as a promising therapeutic approach against type 1 diabetes.

• 出版日期2017-5
• 单位中国药科大学