Intranasal treatment with a recombinant hypoallergenic derivative of the major birch pollen allergen Bet v 1 prevents allergic sensitization and airway inflammation in mice

Background. The major birch pollen allergen Bet v 1 represents one of the m ost prevalent environmental allergens responsible for allergic airway infla mmation. Objective: In the present study we sought to compare the complete recombinant Bet v 1 allergen molecule with genetically produced hypoallerge nic fragments of Bet v 1 regarding mucosal tolerance induction in a mouse m odel of allergic asthma. Methods: BALB/c mice were intranasally treated wit h 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 B et v 1. Results: Intranasal application of F II, containing the major T cel l epitope, led to significant reduction of IgE/IgG1 antibody responses, in vitro cytokine production (IL-5, IFN-gamma, IL-10) and negative immediate c utaneous hypersensitivity reactions comparable to the pre-treatment with th e 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 m olecule was required. The mechanisms leading to immunosuppression seemed to differ in their dependence on the conformation of the molecules, since tol erance induced with the complete Bet v 1, but not with F II, was transferab le with spleen cells and associated with increased TGF-beta mRNA levels. Co nclusion: We conclude that mucosal tolerance induction with recombinant all ergens and genetically engineered hypoallergenic derivatives thereof could provide a convenient and safe intervention strategy against type I allergy. Copyright (C) 2001 S. Karger AG, Basel.