title: Vaccination of non-obese diabetic mice with a fragment of peptide P277 attenuates insulin-dependent diabetes mellitus.
abstract: P277 is a peptide derived from the HSP60 regions, have potent immunological effect on insulin-dependent diabetes mellitus (IDDM) and its phase III clinical trials are currently under investigation. However, we recently discovered a positive correlation between anti-P277 autoantibodies and the presence of endothelial cells damage in inducing vascular leak syndrome. Therefore, the aim of our study was to demonstrate the critical peptide epitope of P277 to IDDM and to highlight the effects of this peptide therapy on inflammation of the islets. Groups of 4-week old female non-obese diabetic (NOD) mice were immunized one time every three weeks for three times with a residue of P277, showing a significant effect of down-regulating immunity to P277 protein and preventing the development of IDDM. Immunologic results including the suppression of T-cell proliferation, the increase of interleukin-10 (IL-10) production and reduction of interferon-γ (IFN-γ) production caused immune tolerance to P277. Hence, a functional role of the key epitope in P277 peptide capable of preventing IDDM is suggested, which could be modified to develop a novel safe and effective peptide vaccine against IDDM by reconstructing P277 in the further studies.
authors.affiliation: Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Ma
authors.forename: Yong
authors.initials: Y
authors.lastname: Lu
authors.forename: Jing
authors.initials: J
authors.lastname: Hou
authors.forename: Yuan-Kai
authors.initials: YK
authors.lastname: Dong
authors.forename: Ming-Zhu
authors.initials: MZ
authors.lastname: Du
authors.forename: Yun
authors.initials: Y
authors.lastname: Xing
authors.forename: Chi-Yu
authors.initials: CY
authors.lastname: Ge
authors.forename: Mao-Lei
authors.initials: ML
authors.lastname: Xu
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.forename: Rong-Yue
authors.initials: RY
authors.lastname: Cao
authors.forename: Tai-Ming
authors.initials: TM
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D018834:Chaperonin 60; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control* / Q000628:therapy; D015536:Down-Regulation / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology; D005260:Female; D006360:Heat-Shock Proteins / Q000008:administration & dosage* / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014611:Vaccination / Q000379:methods
chemical_list: D001323:Autoantibodies; D018834:Chaperonin 60; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; C095402:peptide 277, heat shock protein 60; D016753:Interleukin-10; D007371:Interferon-gamma