Original Paper

Intranasal Treatment with a Recombinant Hypoallergenic Derivative of the Major Birch Pollen Allergen Bet v 1 Prevents Allergic Sensitization and Airway Inflammation in Mice
Ursula Wiedermann^a,b, Udo Herz^d, Karin Baier^b, Susanne Vrtala^b, Ulrich Neuhaus-Steinmetz^d, Barbara Bohle^b, Gerhard Dekan^c, Harald Renz^d, Christof Ebner^b, Rudolf Valenta^b, Dietrich Kraft<sup>b

a</sup>Department of Clinical Pharmacology,
^bDepartment of Pathophysiology and,
^cDepartment of Clinical Pathology, University of Vienna, Austria;
^dClinical Chemistry and Molecular Diagnostics of the Clinicum of the PhilippsUniversity Marburg, Germany

Address of Corresponding Author

Int Arch Allergy Immunol 2001;126:68-77 (DOI: 10.1159/000049496)

  Key Words

• Type I allergy
• Birch pollen
• Bet v 1
• Recombinant hypoallergenic fragments
• Tolerance/suppression
• Mucosa
• Animal model, in vivo
• BALB/c

  Abstract

Background: The major birch pollen allergen Bet v 1 represents one of the most prevalent environmental allergens responsible for allergic airway inflammation. Objective: In the present study we sought to compare the complete recombinant Bet v 1 allergen molecule with genetically produced hypoallergenic fragments of Bet v 1 regarding mucosal tolerance induction in a mouse model of allergic asthma. Methods: BALB/c mice were intranasally treated with recombinant Bet v 1 or with two recombinant Bet v 1 fragments (F I: aa 1-74; F II: aa 75-160) prior to aerosol sensitization with birch pollen and Bet v 1. Results: Intranasal application of F II, containing the major T cell epitope, led to significant reduction of IgE/IgG1 antibody responses, in vitro cytokine production (IL-5, IFN-, IL-10) and negative immediate cutaneous hypersensitivity reactions comparable to the pretreatment with the complete rBet v 1 allergen. Moreover, airway inflammation (eosinophilia, IL-5) was inhibited by the pretreatment with either the complete Bet v 1 or F II. However, for prevention of airway hyperresponsiveness the complete molecule was required. The mechanisms leading to immunosuppression seemed to differ in their dependence on the conformation of the molecules, since tolerance induced with the complete Bet v 1, but not with F II, was transferable with spleen cells and associated with increased TGF- mRNA levels. Conclusion: We conclude that mucosal tolerance induction with recombinant allergens and genetically engineered hypoallergenic derivatives thereof could provide a convenient and safe intervention strategy against type I allergy.

Copyright © 2001 S. Karger AG, Basel

  Author Contacts

Correspondence to: Dr. Ursula Wiedermann, MD, PhD
Department of Clinical Pharmacology, University of Vienna
AKH, Währinger Gürtel 18-20, A-1090 Vienna (Austria)
Tel. +43 1 40400 5132, Fax +43 1 40400 5130
E-Mail ursula.wiedermann@akh-wien.ac.at

  Article Information

Received: Received: March 13, 2001
Accepted: April 2, 2001
Number of Print Pages : 10
Number of Figures : 5, Number of Tables : 0, Number of References : 40