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
| Autor: | Xiaomin Wei, Xiaoran Liu, Li Taiming, Li Zhixin, Rui Jiao, Fang Jinzhi, Yanjie Ma, Peng Cheng |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Blood Glucose
Male 0301 basic medicine medicine.medical_specialty Dipeptidyl Peptidase 4 T-Lymphocytes 030209 endocrinology & metabolism Biology Streptozocin Epitope Dipeptidyl peptidase Diabetes Mellitus Experimental Epitopes Mice 03 medical and health sciences 0302 clinical medicine Glucagon-Like Peptide 1 Internal medicine Diabetes mellitus medicine Animals Humans Immunologic Factors Insulin Dipeptidyl peptidase-4 Cell Proliferation Pharmacology B-Lymphocytes Dipeptidyl-Peptidase IV Inhibitors Vaccines Type 1 diabetes Interleukins Type 2 Diabetes Mellitus Chaperonin 60 General Medicine medicine.disease Streptozotocin Mice Inbred C57BL Diabetes Mellitus Type 1 Glucose 030104 developmental biology Endocrinology Insulitis medicine.drug |
| Zdroj: | Biomedicine & Pharmacotherapy. 89:1467-1475 |
| ISSN: | 0753-3322 |
| DOI: | 10.1016/j.biopha.2017.01.089 |
| Popis: | Type 1 diabetes is a chronic organ-specific autoimmune disease in which selective destruction of insulin-producing β-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-γ 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. |
| Databáze: | OpenAIRE |
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