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Safety


Anaphylactic reactions upon subcutaneous administration of allergens are caused by IgE-binding to the injected allergen. There are two major concepts for improving the safety of SIT. The first of these is to modify the allergen in such way that it exhibits significantly decreased IgE-binding potency, i.e. that it becomes hypo-allergenic. With allergen extracts this has been successfully achieved by chemical modification (e.g. glutaraldehyde). Here for the first time, we will apply this concept to recombinant food allergens. In addition, molecular biology will be used as an alternative approach to attain hypo-allergenicity. Wild-type recombinant allergens will be mutated into hypo-allergenic variants by site-directed mutagenesis.



In the context of this proposal we focus on IgE-mediated food hypersensitivity, hereafter referred to as food allergy. The only available treatment for food allergy is avoidance, in conjunction with rescue medication in case of accidental exposure. Hidden allergens in composite foods or unwanted contaminations and occasional poor adherence to dietary restrictions make avoidance difficult and ineffective. Most food allergies are chronic life-long diseases that are potentially life-threatening. It is the main cause of emergency hospital ward visits for anaphylaxis. Food allergy is estimated to affect around 10 million EU citizens, and the threat of severe anaphylaxis has great impact on the quality of life of patients and their relatives. A curative treatment for food allergy is the only way to change this situation. Allergen-specific immunotherapy (SIT) is the only treatment available that comes close to a cure by targeting the immunological basis of the disease. During classical SIT allergic patients receive monthly injections with allergen extract for three to five years. It is a successful treatment for insect venom allergies and for respiratory allergies like rhino-conjunctivitis to pollen and house dust mite. Despite that almost 95% of the market for treatment of allergic diseases is covered by symptomatic drugs. The burden of monthly injections for prolonged periods and the variable quality of products based on biological extracts provide the basis for the current niche position of SIT. For food allergy, SIT is not used at all. Attempts to treat food allergies by SIT have failed because anaphylactic side-effects were too numerous and severe.