Cytokine and antibody responses in birch-pollen-allergic patients treated with genetically modified derivatives of the major birch pollen allergen Bet v 1

Int Arch Allergy Immunol. 2005 Sep;138(1):59-66. doi: 10.1159/000087358. Epub 2005 Aug 11.

Abstract

Background: Recently, recombinant hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, were used to treat birch-pollen-allergic patients in a double-blind, placebo-controlled, multi-centre immunotherapy study. The aim of this study was to evaluate the effects of vaccination with aluminium-hydroxide-adsorbed recombinant Bet v 1 derivatives versus placebo on T-cell, cytokine and antibody responses in a subgroup of patients.

Methods: Blood was drawn from patients of the Swedish centre (n = 27; rBet v 1 fragments: n = 10; rBet v 1 trimer: n = 8, and placebo-aluminium hydroxide: n = 9) before the start and after completion of the treatment. PBMC were stimulated with rBet v 1 and analysed for cytokine (IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-gamma)-secreting cells by ELISpot. Bet v 1-specific antibody levels in serum (IgG(1-4), IgE and IgA) were measured by ELISA. Skin prick tests with defined Bet v 1 concentrations were performed before and 10-11 months after the beginning of the study.

Results: Bet v 1-specific IgG levels, consisting of IgG(1), IgG(2) and IgG(4), were significantly increased after treatment with recombinant allergen derivatives. Treatment with rBet v 1 trimer led to a significant (p < 0.05) reduction of Bet v 1-reactive IL-5- and IL-13-producing cells, reflecting a reduced Th2 response. In addition, a decreased number of Bet v 1-reactive IL-4 producing (p = 0.07) and an increase of IL-12-producing (p = 0.06) cells was noted in the trimer-treated patients. In contrast to placebo, active treatment resulted in significantly reduced immediate-type skin reactions to Bet v 1 even 10-11 months after treatment.

Conclusion: Vaccination with recombinant hypoallergenic Bet v 1 derivatives induces a Bet v 1-specific IgG response and leads to reduced skin reactivity in allergic patients. A reduction of Bet v 1-specific Th2 responses was observed in trimer-treated patients, which may reflect the intrinsic property of this allergen derivative.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Allergens / genetics
  • Allergens / immunology
  • Allergens / therapeutic use
  • Antibodies / blood
  • Antibodies / drug effects*
  • Antibodies / immunology
  • Betula / immunology
  • Cells, Cultured
  • Cytokines / blood
  • Cytokines / drug effects*
  • Cytokines / immunology
  • Desensitization, Immunologic / methods*
  • Double-Blind Method
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Hypersensitivity, Immediate / drug therapy*
  • Hypersensitivity, Immediate / immunology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Plant Proteins / genetics
  • Plant Proteins / immunology
  • Plant Proteins / therapeutic use*
  • Pollen / immunology
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use*
  • Skin Tests

Substances

  • Allergens
  • Antibodies
  • Cytokines
  • Plant Proteins
  • Recombinant Proteins