Project 08

Heimo Breiteneder, Dept. of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna.

Project 08: Recombinant allergen derivatives and adjuvants to direct dendritic cells

Heimo Breiteneder has worked for more than 25 years in allergy research. He has a strong expertise regarding the molecular characterization of allergens and developed classification systems for allergens. Based on the recent notion that different allergens and allergen isoforms impact in a different manner on antigen presenting cells, he now asks, whether it is possible to redirect allergen-specific immune responses with allergen-derivatives at the level of antigen recognition and which genes are involved. He will expose immature MoDCs from allergic and non-allergic donors to the allergens Bet v 1, Der p 2 (house dust mite), and Pru p 3 (peach). Chimeric proteins of allergens and non-allergenic structural homologues will be used to delineate allergen-associated molecular patterns and their structures will be determined. Allergens irrelevant for the respective donors will be included as controls. Following stimulation, gene expression profiles will be analyzed by real time PCR and pathway gene arrays. The ability of the allergens and chimeric proteins to induce specific polarizations of the Th cell response will be determined. Gene expression data associated with allergic sensitization will be verified by exposure to allergens of DCs transiently transfected with siRNAs specific for mRNAs of selected genes. The influence of LPS and pollen-associated lipid mediators on gene expression patterns will also be assessed. Other goals are to evaluate allergen-specific prophylactic and mimotope-based vaccines as well as the effects of adjuvants on the polarization of Th cell responses in the DC-T cell co-culture system. DC gene expression profiles following exposure to the vaccine candidates will be determined and compared to the established gene signatures. Likewise, the impact of IgG blocking antibodies in conjunction with the allergens on DC gene expression and polarization of Th cell responses will be analyzed. The project will thus contribute to the understanding of the pathomechanisms of allergic sensitization. By defining disease relevant gene signatures it will become possible to therapeutically exploit the underlying pathways and to evaluate new allergy vaccines.

Heimo Breiteneder, Ph.D.
Professor of Medical Biotechnology
Head, Division of Medical Biotechnology
Chairman, I.U.I.S. allergen nomenclature sub-committee
Department of Pathophysiology and Allergy Research
Center for Pathophysiology, Infectiology & Immunology
Medical University of Vienna
Waehringer Guertel 18-20, AKH-EBO-3Q
Vienna, 1090 Austria
Tel.: +431-40400-51020; Fax : +431-40400-51300

Publications:

Bublin, M., M. Kostadinova, C. Radauer, C. Hafner, Z. Szépfalusi, E. M. Varga, S. J. Maleki, K. Hoffmann-Sommergruber, and H. Breiteneder H. 2013. IgE cross-reactivity between the major peanut allergen Ara h 2 and the non-homologous allergens Ara h 1 and Ara h 3. J. Allergy Clin. Immunol. Mar 2. [Epub ahead of print] DOI: 10.1016/j.jaci.2013.01.022

Chruszcz, M., S. J. Maleki, K. A. Majorek, M. Demas, M., Bublin, R. Solberg, B. K. Hurlburt, S. Ruan, C. B. Mattison, H. Breiteneder, and W. Minor. 2011. Structural and immunologic characterization of Ara h 1 – a major peanut allergen. J. Biol. Chem. 286(45): 39318-39327. DOI: 10.1074/jbc.M111.270132

Smole, U., S. Wagner, N. Balazs, C. Radauer, M. Bublin, G. Allmaier, K. Hoffmann-Sommergruber, and H. Breiteneder. 2010. Bet v 1 and its homologous food allergen Api g 1 stimulate dendritic cells from birch pollen-allergic individuals to induce different Th-cell polarization. Allergy 65:1388-1396. DOI: 10.1111/j.1398-9995.2010.02407.x

Radauer, C., P. Lackner, and H. Breiteneder. 2008. The Bet v 1 fold: an ancient, versatile scaffold for binding of large, hydrophobic ligands. BMC Evol. Biol. 8: 286. DOI: 10.1186/1471-2148-8-286

Radauer, C., M. Bublin, S. Wagner, A. Mari, and H. Breiteneder. 2008. Allergens are distributed into few protein families and possess a restricted number of biochemical functions. J. Allergy Clin. Immunol. 121: 847-852. DOI: 10.1016/j.jaci.2008.01.025