A rationally designed peptide IA-2-P2 against type 1 diabetes in streptozotocin-induced diabetic mice

Diab Vasc Dis Res. 2017 May;14(3):184-190. doi: 10.1177/1479164116664189. Epub 2017 Mar 1.

Abstract

Recent studies have investigated the potential of type 1 diabetes mellitus-related autoantigens, such as heat shock protein 60, to induce immunological tolerance or to suppress the immune response. A functional 24-residue peptide derived from heat shock protein 60 (P277) has shown anti-type 1 diabetes mellitus potential in experimental animals and in clinical studies, but it also carries a potential atherogenic effect. In this study, we have modified P277 to retain an anti-type 1 diabetes mellitus effect and minimize the atherogenic potential by replacing the P277 B epitope with another diabetes-associated autoantigen, insulinoma antigen-2 (IA-2), to create the fusion peptide IA-2-P2. In streptozotocin-induced diabetic C57BL/6J mice, the IA-2-P2 peptide displayed similar anti-diabetic effects to the control P277 peptide. Also, the IA-2-P2 peptide did not show atherogenic activity in a rabbit model. Our findings indicate the potential of IA-2-P2 as a promising vaccine against type 1 diabetes mellitus.

Keywords: Type 1 diabetes; atherosclerosis; insulinoma antigen-2; peptide P277.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / chemically induced
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chaperonin 60 / administration & dosage
  • Chaperonin 60 / pharmacology*
  • Chaperonin 60 / toxicity
  • Cytokines / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / immunology
  • Drug Design*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / toxicity
  • Immunization
  • Lymphocyte Activation / drug effects
  • Male
  • Mice, Inbred C57BL
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / toxicity
  • Rabbits
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / administration & dosage
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / pharmacology*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / toxicity
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / pharmacology*
  • Recombinant Fusion Proteins / toxicity
  • Streptozocin
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Time Factors
  • Vaccines / administration & dosage
  • Vaccines / pharmacology*
  • Vaccines / toxicity

Substances

  • Blood Glucose
  • Chaperonin 60
  • Cytokines
  • Hypoglycemic Agents
  • IA-2-P2 peptide
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Vaccines
  • peptide 277, heat shock protein 60
  • Streptozocin
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8