Carrier-bound nonallergenic Der p 2 peptides induce IgG antibodies blocking allergen-induced basophil activation in allergic patients

Allergy. 2012 May;67(5):609-21. doi: 10.1111/j.1398-9995.2012.02794.x. Epub 2012 Feb 17.

Abstract

Background: More than 90% of house dust mite-allergic patients are sensitized to the major Dermatophagoides pteronyssinus allergen, Der p 2. The aim of this study was to develop and characterize an allergy vaccine based on carrier-bound Der p 2 peptides, which should allow reducing IgE- and T-cell-mediated side-effects during specific immunotherapy (SIT).

Methods: Five Der p 2 peptides (P1-P5) were synthesized and analyzed regarding IgE reactivity and allergenic activity. Lymphoproliferative and cytokine responses induced with Der p 2 and Der p 2 peptides were determined in peripheral blood mononuclear cells from mite-allergic patients. Der p 2-specific IgG antibodies induced with carrier-bound Der p 2 peptides in mice and rabbits were tested for their capacity to inhibit IgE binding and basophil activation in allergic patients.

Results: Of five overlapping peptides (P1-P5) covering the Der p 2 sequence, two peptides (P2 and P4) were identified, which showed no relevant IgE reactivity, allergenic activity, and induced lower Der p 2-specific T-cell activation than Der p 2. However, when coupled to a carrier, P2 and P4 induced Der p 2-specific IgG antibodies in animals, which inhibited allergic patients' IgE binding to the allergen and allergen-induced basophil activation similar as antibodies induced with Der p 2.

Conclusions: Carrier-bound Der p 2 peptides should allow avoiding IgE-mediated side-effects, and because of their low potential to activate allergen-specific T cells, they may reduce late-phase side-effects during SIT. Further, these peptides may be also useful for prophylactic vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology*
  • Amino Acid Sequence
  • Animals
  • Antibodies, Blocking / immunology*
  • Antibody Specificity / immunology
  • Antigens, Dermatophagoides / chemistry
  • Antigens, Dermatophagoides / immunology*
  • Arthropod Proteins / chemistry
  • Arthropod Proteins / immunology*
  • Basophils / immunology*
  • Basophils / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • Female
  • Hemocyanins / chemistry
  • Humans
  • Hypersensitivity / immunology*
  • Immunoglobulin E / immunology
  • Immunoglobulin E / metabolism
  • Immunoglobulin G / immunology*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / immunology*
  • Phosphoric Diester Hydrolases / metabolism
  • Protein Binding / immunology
  • Pyroglyphidae / immunology
  • Pyrophosphatases / antagonists & inhibitors
  • Pyrophosphatases / metabolism
  • Rabbits
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Vaccines, Conjugate / immunology

Substances

  • Allergens
  • Antibodies, Blocking
  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Cytokines
  • Dermatophagoides pteronyssinus antigen p 2
  • ENPP3 protein, human
  • Immunoglobulin G
  • Peptides
  • Vaccines, Conjugate
  • Immunoglobulin E
  • Hemocyanins
  • Phosphoric Diester Hydrolases
  • Pyrophosphatases
  • keyhole-limpet hemocyanin