Oral Administration of Recombinant Live Yeast Producing Altered Peptide Ligand Derived from Insulin B:9-23 Peptide Linked to Cholera Toxin B Subunit Suppresses Development of Autoimmune Diabetes in NOD Mice

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概要

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• Insulin is a major autoantigen responsible for the pathogenesis of type 1 diabetes, and its B-chain peptide B:9-23 has been suggested to contain critically important epitopes in the NOD mouse. We have previously demonstrated that the altered peptide ligand of B:9-23 peptide with alanine substitutions at positions 16 and 19 (A16,19 APL) suppresses insulitis and reduces the incidence of diabetes when administered intranasally together with cholera toxin (CT). In this study, we extended the previous findings to determine whether mucosal administration of the A16,19APL without the use of toxic CT is efficacious for diabetes prevention. To this end,we linked the A16,19APL to the C-terminus of non-toxic cholera toxin (CTB) B subunit and the chimeric fusion protein was produced in methyloprophic yeast Pichia pastoris. Although intranasal administration of the recombinant CTB-A16,19APL fusion protein extracted fromthe yeast cells failed to prevent the progression to diabetes, oral administration of the live yeast cells producing the chimeric protein resulted in more than 50% reduction of the development of diabetes, albeit the fact that protective efficacy did not reach the significance level by life table analysis (P= 0.08). Furthermore, the expression of insulin autoantibodies was not altered throughout the course of oral immunization experiment. These results demonstrated that the efficacy of recombinant CTB-A16,19APL for oral immunization has much room for improvement. Nevertheless, oral administration of recombinant yeast or other edible materials such as food plants engineered to produce altered autoantigenic peptide could potentially become a novel non-invasive immunotherapeutic strategy for type 1 diabetes. (250 word)

著者

• Zhou Hongbo

  Department of Endocrinology and Metabolism, Unit of Translational Medicine, Nagasaki University Grad

• Arakawa Takeshi

  Molecular Microbiology Group, Tropical Biosphere Research Center, University of the Ryukyus

• Sakima Rina

  Department of Parasitology, Graduate School of Medicine, University of the Ryukyus

• Kawasaki Eiji

  Metabolism-Diabetes and Clinical Nutrition, Nagasaki University Hospital

• Yamasaki Hironori.

  Health Center, Nagasaki Unive rsity

• Zhou Hongbo

  Department Of Endocrinology And Metabolism Unit Of Translational Medicine Nagasaki University Gradua

• Sakima Rina

  Department Of Parasitology Graduate School Of Medicine University Of The Ryukyus

• Kawasaki Eiji

  Metabolism-diabetes And Clinical Nutrition Nagasaki University Hospital

• Arakawa Takeshi

  Molecular Microbiology Group Tropical Biosphere Research Center University Of The Ryukyus

• Yamasaki Hironori.

  Health Center Nagasaki Unive Rsity

• Arakawa Takeshi

  Molecular Microbiology Group Department Of Tropical Infectious Diseases Center Of Molecular Bioscien

• Abiru Norio

  Molecular Microbiology Group, Tropical Biosphere Research Center, University of the Ryukyus

• Arakawa Takeshi

  Department of Parasitology, Graduate School of Medicine, University of the Ryukyus

• Sakima Rina

  Metabolism-Diabetes and Clinical Nutrition, Nagasaki University Hospital

• Miyata Takeshi

  Health Center, Nagasaki Unive rsity

関連論文

• Oral Administration of Recombinant Live Yeast Producing Altered Peptide Ligand Derived from Insulin B:9-23 Peptide Linked to Cholera Toxin B Subunit Suppresses Development of Autoimmune Diabetes in NOD Mice
• Suppressed induction of mycobacterial antigen-specific T_h1-type CD4^+ T cells in the lung after pulmonary mycobacterial infection
• Expression and Secretion of Cholera Toxin B Subunit in Lactobacilli

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