CRM197-Coupled Der p 2 Peptides Suppress Allergic Airway Inflammation in a Der p 2-Induced Asthma Mouse Model

Int Arch Allergy Immunol. 2019;180(3):173-181. doi: 10.1159/000502607. Epub 2019 Sep 19.

Abstract

Allergic diseases affect more than 25% of the global population. Der p 2 is the major allergen of the house dust mite (HDM) Dermatophagoides pteronyssinus. Allergen-specific immunotherapy is the only treatment to change the course of allergic diseases. In this study, two synthesized Der p 2 peptides coupled to cross-reacting material 197 (CRM197) showed reduced IgE reactivity and allergenic activity. CRM197-coupled Der p 2 peptides induced rDer p 2-specific IgG1 antibodies in mice, which could inhibit HDM-allergic patients' IgE binding to rDer p 2. The immunity effects of CRM197-coupled Der p 2 peptides were studied in an rDer p 2-induced asthma mouse model. CRM197-coupled Der p 2 peptides can suppress asthmatic airway inflammation in this model. Analysis of IL-4, IL-5, and IFN-γ levels in bronchoalveolar lavage fluid revealed that the suppression was associated with a shift from a Th2 to a Th1 response. Thus, CRM197-bound Der p 2 peptides exhibited less allergenic activity than the rDer p 2 allergen, which preserved immunogenicity and may be candidates for mite allergy vaccines.

Keywords: Allergen-specific immunotherapy; Cross-reacting material 197; Der p 2; House dust mite; Mouse model of asthma.

MeSH terms

  • Animals
  • Antigens, Dermatophagoides / chemistry
  • Antigens, Dermatophagoides / immunology*
  • Arthropod Proteins / chemistry
  • Arthropod Proteins / immunology*
  • Asthma / immunology
  • Asthma / therapy*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / immunology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Immunoglobulin E / metabolism
  • Immunoglobulin G / metabolism
  • Inflammation / immunology
  • Inflammation / therapy*
  • Lung / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Peptides / chemistry
  • Peptides / immunology*
  • Respiratory Hypersensitivity / immunology
  • Respiratory Hypersensitivity / therapy*
  • Th1-Th2 Balance
  • Vaccines / immunology

Substances

  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Bacterial Proteins
  • Cytokines
  • Dermatophagoides pteronyssinus antigen p 2
  • Immunoglobulin G
  • Peptides
  • Vaccines
  • CRM197 (non-toxic variant of diphtheria toxin)
  • Immunoglobulin E