Allergen-specific antibodies for therapy of Type I allergy

Type I allergy is an immunoglobulin E (IgE)-mediated hypersensitivity disease induced by allergen contact which affects more than 25% of the population. The immediate symptoms (e.g., allergic rhinoconjunctivitis, asthma) of Type I allergy are induced by allergen-mediated crosslinking of effector cells (e.g. mast cells, basophils)-bound IgE antibodies and the subsequent release of inflammatory mediators (e.g. histamine). Results of several recent studies demonstrate that allergen-specific IgG antibodies are potent antagonists of IgE-mediated immune reactions and have rekindled the interest in their potential therapeutic application. The aim of this project is to identify and characterize IgG antibodies which antagonize the IgE-mediated reactions to grass and birch pollen allergens. Recombinant major grass and birch pollen allergens containing most of the IgE epitopes of grass and birch pollen will be used to identify suitable antibodies. Human antibodies will be obtained by classical tissue culture technique or by combinatorial cloning and will then be converted by recombinant technology into human IgG antibodies. The inhibition of allergen-induced effector cell (i.e., mast cell/basophil, T cell) activation by the recombinant allergen- specific antibodies will be analyzed using in vitro assays. Furthermore a system using in vitro cultured nasal biopsies from allergic patients will be used to study the anti-allergic effects of the antibodies in situ and methods will be developed to improve the therapeutic efficacy of the antibodies by targeting to epithelial cells. Ultimate goal of the project is to evaluate the potential therapeutic usefulness of allergen-specific IgG antibodies in allergic patients by studying their effects in skin test and nasal provocation studies.