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Division of Immunopathology
Department of Pathophysiology and Allergy Research
Center of Pathophysiology, Infectiology & Immunology

Medical University of Vienna

Vienna General Hospital, AKH, 3Q
Waehringer Guertel 18-20
A-1090 Vienna, Austria
 

Molecular, immunological and structural characterization, and modifications of plant-food and latex allergens for diagnosis, prevention and specific immunotherapy [Breiteneder]

Plant food allergies are on the increase worldwide, tree nut and peanut allergies being clinically associated with severe systemic reactions. Consequently, there is a need to accurately detect and trace allergen levels in foods and foodstuffs, to provide purified allergens for component resolved diagnosis and to develop allergy vaccines. Kiwifruits, macadamia nuts, peanuts, and citrus fruits are rapidly becoming emerging allergen sources across Europe. We will isolate and characterize relevant allergens from these sources and incorporate the purified allergens into existing allergen microarrays for the diagnosis of food allergy. We will establish detection kits that are able to identify these allergens in a complex food matrix based on allergen-specific single chain antibodies selected by phage display technology. These single chain antibodies will further be used to define the topography of IgE epitopes on allergenic 2S albumins, especially Ara h 2 from peanut, by enhanced hydrogen/deuterium exchange mass spectrometry and by co-crystallization. A better understanding of the interaction of these allergens with dendritic cells (DCs) from atopic and non-atopic donors and their role in the generation of allergy will also have an impact on allergy vaccine design. During the previous funding period we have established human DC cultures and revealed differences in the uptake of allergenic and hypoallergenic Bet v 1 isoforms by DCs from allergic and non-allergic donors. We will now examine in detail the effect of complete food allergens (i.e. 2S albumins; Ara h 2 from peanut, Jug r 1 from walnut, SFA8 from sunflower seeds) and incomplete food allergens (i.e. Bet v 1 homologues; Mal d 1 from apple, Cor a 1 from hazelnut, Api g 1 from celery, Dau c 1 from carrot) on monocyte-derived DCs. For vaccine design, we will produce hypoallergenic variants of Ara h 2 reported as the most potent and relevant peanut allergen and other relevant candidate plant food allergens discovered in the course of the project. In a different approach to allergy vaccine design, we will fuse immunodominant T cell epitope peptides of the birch pollen allergen Bet v 1 and of relevant Phleum pratense pollen allergens to the non-toxic subunit B of cholera toxin to be applied as mucosal adjuvant for the improvement of poly-tolerance induction.