Project 07
Sabine Flicker, Dept. of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna.
Project 07: Allergen-specific antibodies for therapy and prevention of allergy.
Sabine Flicker has a strong expertise in the analysis of allergen-specific antibodies and their interaction with allergens as potential target for therapeutic intervention. She has received the Hertha-Firnberg Award of the FWF for her work, which allowed her to form a research group dedicated to the characterization of allergen-specific antibodies. Within the SFB she wants to develop allergen-specific therapeutic antibodies and plans to explore them in vitro, in experimental animal models and finally in vivo. She will generate ScFv libraries of initially grass and birch pollen allergic patients and later from patients with HDM and food allergy and isolate allergen-specific scFvs by panning to purified allergens. ScFvs will be assessed for their specificity, cross-reactivity, affinity and ability to inhibit IgE binding of patients to the allergen. ScFvs which possess inhibitory potential will be converted into complete IgG antibodies and studied for their ability to inhibit IgE-induced basophil degranulation. The potential of the allergen-specific IgG antibodies for treatment and prevention of allergy will be determined in experimental mouse models. The structure of selected antibody/allergen complexes will be determined for a possible structural refinement of antibodies with therapeutic potential and to understand the mechanism of IgE competition. The ability of defined allergen/IgG immune complexes to influence antigen presentation and polarization of T cell responses will be also studied. The ultimate goal is the clinical evaluation of certain allergen-specific IgG antibodies to inhibit allergic inflammation in allergic patients (e.g., skin- and nasal provocation tests).
Sabine Flicker, PhD
Department of Pathophysiology and Allergy Research
Center for Pathophysiology, Infectiology & Immunology
Medical University of Vienna
General Hospital of Vienna
Waehringer Guertel 18-20
1090 Vienna, Austria
tel. +43-1-40400-51150
fax. +43-1-40400-51300
mail.
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Publications:
Padavattan, S., S. Flicker, C. Madritsch, S. Randow, G. Reese, S. Vieths, C. Lupinek, C. Ebner, R. Valenta, Z. Housley-Markovic. 2009. High-affinity IgE recognition of a conformational epitope of the major respiratory allergen Phl p 2, as revealed by X-ray crystallography. J. Immunol. 182: 2141-2151.
Flicker, S., K. Marth, H. Kofler, R. Valenta. 2009. Placental transfer of allergen-specific IgG but not IgE from a SIT-treated mother. J. Allergy Clin. Immunol. 124: 1358-1360.
Madritsch, C., S. Flicker, S. Scheiblhofer, D. Zafred, J.Thalhamer, W. Keller, R. Valenta. 2011. Recombinant monoclonal human IgE to investigate the allergenic activity of major grass pollen allergen, Phl p 5. Clin. Exp. Allergy 41: 270-80.
Gadermaier, E., S. Flicker, P. Steinberger, R. Valenta. Determination of allergen-specificity by heavy chains in grass pollen allergen-specific IgE antibodies. 2012. J. Allergy Clin. Immunol. pii: S0091-6749(12)01621-1. doi: 10.1016/j.jaci.2012.10.010
Flicker, S., B. Linhart, C. Wild, U. Wiedermann, R. Valenta. 2012. Passive immunization with allergen-specific IgG antibodies for treatment and prevention of allergy. Immunobiol. pii: S0171-2985(12)00518-9. doi: 10.1016/j.imbio.2012.10.008.
