Goals of the SFB
Major research topics
Meetings & Seminars
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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

Major research topics

Topic1: Molecular, structural and immunological characterization of environmental allergens

Topic 1 is dedicated to the characterization of important allergens by recombinant DNA technology. During the last years an increasing panel of recombinant allergens which mimick the structural and immunological properties of their natural counterparts has been produced in several laboratories. A major goal of this SFB is to contribute to the completion of the growing body of recombinant allergens to be used for diagnostic and therapeutic application. For this purpose three groups (#2-4) will continue to characterize allergens from important allergen sources (plant food, latex, animals, mites) to establish as complete as possible panels of recombinant allergens from these sources. The groups have a long experience in the field of molecular allergen characterization and production of recombinant allergens but must interact with structural biology experts (group #5), experts in animal models (group #13, 14) and clinicians (groups #10, 11, 12) in order to achieve biological characterization of the recombinant allergen molecules. Their goals are the immunological (in vitro: epitope mapping, cellular reactivity: collaborations with projects #6, 7, 8, 9; in vivo: project #13, 14), structural (determination of three-dimensional allergen structures in collaboration with project #5) and clinical characterization (collaboration with projects #10, 11, 12) of the recombinant allergens and their epitopes. The groups involved in allergen characterization will also produce allergen-specific antibodies and synthetic ligands in collaboration with project #8, to obtain probes for environmental allergen analysis. The overlapping and complementary expertises of the SFB project partners (molecular biology, structural biology, protein chemistry, immunology, clinical experience) will allow the efficient production and characterization of as complete as possible allergen panels from plant-foods, latex, animals and mites. The completion of allergen panels from tree and grass pollens is pursued by the SFB coordinator. Results and reagents will be made available to all SFB participants and there will be close scientific interaction. Another research program coordinated by Dr. Fatima Ferreira from the University of Salzburg is currently working on the characterization of weed and mold allergens. The proposed SFB thus complements work in the field of allergen characterization ongoing in Austria.

Topic 2: Allergen-encounter, uptake, processing: maintenance and modulation of the allergic immune response

The second topic focuses on the analysis of allergen-encounter, uptake, processing and immune responses in the target organs of atopy (respiratory tract, skin, gastrointestinal tract) (projects #11, 12, 13, 14). For this purpose defined recombinant allergens, their epitopes and corresponding human antibodies which have already been produced by the groups working in the field of allergen characterization and those allergens which will be produced in topic 1 will be used to study by in vitro systems (projects #6, 7, 8, 9, 10, 11, 12, 14) but mainly in vivo and in situ (projects #11, 12, 13, 14) allergen-processing and local as well as systemic allergen-specific immune responses. It should be emphasized that the major part of the investigations will be carried out with defined allergen molecules, their epitopes and highly specific probes to provide detailed insight in the operative pathomechanisms. Another aspect of this topic is that allergen-specific immune responses will be studied in the time course of disease. For this purpose immune responses will be analyzed with defined molecules during pregnancy, infancy and in adults. Furthermore, the evolution of the atopic immune response will be studied in infants and adults by projects #7, 10, 11 and 12. Studies concerning the in utero sensitization will be carried out by projects #10 and 14 in mouse models for Type I allergy. In addition, project #10 has developed a placenta model to study transplacental priming of the immune system. Projects #11 and 12 will study the effects of allergen exposure during the natural course of disease and also analyze the influence of various forms of therapy (e. g., allergen-specific immunotherapy, steroids, immunosuppressive-, anti-IgE therapy) on allergen-specific immune responses. Third, allergen-specific immune responses will be studied at the cellular and subcellular level. Allergen presentation will be studied in particular by projects #6, 12 and 13, allergen-specific T cell responses will be analyzed by project #7, allergen-specific humoral immune responses are focus of project #8, and allergen-specific effector cell activation is subject of project #9.

Topic 3: Component-resolved in vitro and in vivo allergy diagnostics for monitoring the development of allergic disease, allergen exposure, disease progression, and therapy

The efforts of the proposed SFB project (output of projects #2, 3, 4) together with complementary work carried out by the coordinator and other Austrian groups should allow to establish panels of recombinant allergens which resemble the IgE epitope repertoire of the most relevant allergen sources to establish new forms of in vitro and in vivo diagnosis. Regarding in vitro allergy diagnosis the aim is to use allergen components and their epitopes to develop microarray-based diagnostics. This aspect will be pursued especially by project #4 which disposes about facilities for the creation and analysis of microarrays. Particular emphasis will be placed to analyze with defined recombinant allergens the association of serological tests and cellular reactivity with in vivo sensitivity. Regarding this aspect the input of projects #4, 7, 8, 9, 10, 11, and 12 will be required. For example, it will be studied how the serum levels of allergen-specific IgE determined by different ways of specific IgE detection (#4) and quantification correlate with cellular tests (e. g., basophil histamine release: project #9) and clinical sensitivity (skin prick-, nasal provocation testing: projects #11, 12). Furthermore we are interested to learn whether the magnitude of proliferative responses by PBMC to certain allergens is associated with the frequency of T cell-mediated late phase manifestations (projects #6, 7, 10, 11, 12). In addition to classical assays, the usefulness of activation markers on effector cells for studying effector cell activation and the release of cytokines from T cells will be studied (projects #7, 9). One major theme is thus to use defined recombinant allergens for the refinement of serological, cellular and in vivo allergy testing. In another approach the newly developed diagnostics should be used for refined serological and cellular analysis of the development of allergic disease, of different disease manifestations (acute, chronic disease), in untreated and treated patients (projects #10, 11, 12).

Topic 4: Genetic engineering and synthesis of hypoallergenic allergen derivatives, evaluation of new adjuvants, vaccination and tolerance-induction protocols

The development of novel treatment strategies requires basic work regarding allergen-characterization in vitro, in experimental animal models and in patients. The proposed SFB thus combines groups which will work on the preparation of vaccine candidates by molecular biology and synthetic peptide chemistry (projects #2, 3, 4, 8). These groups will receive assistance by a structural biology group (project #5) and by groups working on the in vitro immunological characterization of the new vaccine candidates (projects #6, 7, 9). The produced allergen-derivatives will then be evaluated in vivo in experimental animal models for Type I allergy (project #13, 14) and regarding in vivo safety by provocation (skin testing, nasal provocation testing) in allergic patients by the clinical investigators (projects #10, 11, 12). Major goal of this topic is to produce and evaluate vaccine candidates, adjuvants and treatment protocols for allergies to the most important allergen sources which can then be studied in first clinical trials. Topic 4: Clinical evaluation of novel treatment strategies The proposed SFB includes clinical groups with a long lasting experience regarding the performance of specific immunotherapy trials and the clinical evaluation of other treatment strategies for Type I allergy (projects #10, 11, 12). Moreover projects #10, 14 will perform the clinical evaluation of tolerance induction protocols in early infancy. The clinical investigators included in this SFB are further able to perform in vivo provocation analysis (e.g., skin prick-, intradermal testing, nasal provocation testing, food challenge testing). It will thus be possible to evaluate safety and efficacy of novel treatment strategies in the proposed SFB program.