title: 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.
abstract: 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.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Jinzhi
authors.initials: J
authors.lastname: Fang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Jiao
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wei
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Ma
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, PR China. Electronic address: taimingli@163.com.
authors.forename: Taiming
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001786:Blood Glucose / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D018834:Chaperonin 60 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D000939:Epitopes / Q000276:immunology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology*; D007328:Insulin / Q000097:blood; D007378:Interleukins / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013311:Streptozocin / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014612:Vaccines / Q000276:immunology*
chemical_list: D001786:Blood Glucose; D018834:Chaperonin 60; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000939:Epitopes; D007155:Immunologic Factors; D007328:Insulin; D007378:Interleukins; D014612:Vaccines; D013311:Streptozocin; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4; D005947:Glucose
keywords: Antibody; Autoantigens; Diabetes; Dipeptidyl peptidase 4; β-cell