Nasal challenges with recombinant derivatives of the major birch pollen allergen Bet v 1 induce fewer symptoms and lower mediator release than rBet v 1 wild-type in patients with allergic rhinitis

Clin Exp Allergy. 2002 Oct;32(10):1448-53. doi: 10.1046/j.1365-2745.2002.01495.x.

Abstract

Background: Genetic engineering of the major birch pollen allergen (Bet v 1) has led to the generation of recombinant Bet v 1 derivatives with markedly reduced IgE-binding capacity, but with retained T cell activating ability.

Objective: To compare the mucosal reactivity to rBet v 1 derivatives with rBet v 1 wild-type as basis for new therapeutic strategies for birch pollen allergy based on mucosal tolerance induction.

Methods: Outside the pollen season, 10 patients with birch pollen allergic rhinitis and mild asthma underwent four nasal challenge-sessions in a randomized, double-blind, and cross-over design, employing increasing doses of rBet v 1 fragment mix, rBet v 1 trimer, rBet v 1 wild-type and diluent (albumin). Nasal lavage fluids (NAL) were collected before the challenge-series as well as 10 min, 4 and 24 h thereafter. Nasal lavage fluid levels of tryptase as well as EPO and ECP were measured as indices of mast cell and eosinophil activity, respectively.

Results: All 10 patients tolerated the highest accumulated dose, 8.124 microg, when challenged with rBet v 1 trimer, eight with rBet v 1 fragments compared to one when challenged with rBet v 1 wild-type. No late phase reactions were observed. The change in tryptase levels (pre-challenge vs. 10 min) was significantly lower after challenges with rBet v 1 trimer and rBet v 1 fragments than with rBet v 1 wild-type. The change in EPO/ECP concentration pre-challenge versus 4 h post-challenge was lower for rBet v 1 trimer and the change was significantly lower when pre-challenge versus 24 h post-challenge to rBet v 1 fragments and rBet v 1 wild-type was examined.

Conclusion: The derivatives induced significantly fewer symptoms and lower mast cell and eosinophil activation than rBet v 1 wild-type upon application to the nasal mucosa. They could in the future be candidates for immunotherapy based on mucosal tolerance induction.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens*
  • Analysis of Variance
  • Antigens, Plant
  • Betula*
  • Cross-Over Studies
  • Double-Blind Method
  • Eosinophil Peroxidase
  • Female
  • Humans
  • Inflammation Mediators / analysis
  • Male
  • Nasal Lavage Fluid / chemistry
  • Nasal Mucosa / enzymology
  • Nasal Mucosa / immunology*
  • Nasal Provocation Tests
  • Peroxidases / analysis
  • Plant Proteins*
  • Pollen*
  • Recombinant Proteins / administration & dosage
  • Rhinitis, Allergic, Perennial / enzymology
  • Rhinitis, Allergic, Perennial / immunology*
  • Serine Endopeptidases / analysis
  • Statistics, Nonparametric
  • Tryptases

Substances

  • Allergens
  • Antigens, Plant
  • Inflammation Mediators
  • Plant Proteins
  • Recombinant Proteins
  • Bet v 1 allergen, Betula
  • Eosinophil Peroxidase
  • Peroxidases
  • Serine Endopeptidases
  • Tryptases