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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 of mite allergens for diagnosis, pre-vention and specific immunotherapy. [Vrtala]

Project summary

The major aims of project F01803 are the molecular characterization of house dust mite allergens, the selection of the allergens necessary for diagnosis and therapy and the construction of hypoallergenic derivatives of mite allergens for improved immunotherapy. These projects should lead to the improvement of diagnosis and therapy of mite allergic patients.
In the last project period of this SFB, we showed that commercially available mite extracts show a great variability regarding the content of the major mite allergens, Der p 1 and Der p 2, and that most of the other important mite allergens are underrepresented in the extracts. Therefore, we have constructed a Dermatophagoides pteronyssinus expression cDNA library to isolate cDNA clones coding for the most important mite allergens in order to obtain the spectrum of house dust mite allergens. We isolated four cDNA clones coding for new mite allergens which were expressed in E. coli and purified to homogeneity. We have started to characterize these allergens and we plan to continue the molecular characterization in the new project period. Additionally, we have expressed in E. coli and purified the most important house dust mite allergens (rDer p 2, rDer p 5, rDer p 7 and rDer p 10). The panel of recombinant Dermatophagoides pteronyssinus allergens that we have now available will allow us to study the importance of the individual allergens regarding their clinical relevance and to determine the panel of relevant Dermatophagoides pteronyssinus allergens for immunotherapy of mite allergic patients.
These allergens will be modified into hypoallergenic derivatives. In the first two project periods of this SFB, we have constructed hypoallergenic derivatives of the major mite allergens, Der p 1 and Der p 2. Hypoallergenic derivatives of Der p 2 were produced which contain the major T-cell epitopes and induce blocking IgG responses in experimental animal models. Furthermore, non-allergenic fragments of Der p 1 and Der p 2 were defined which should allow to assemble hypoallergenic mosaic molecules for Der p 1 and Der p 2. We also plan to construct hypoallergenic derivatives of other important Dermatophagoides pteronyssinus allergens (e.g., Der p 5, Der p 7, clone 30-derived allergen) and to continue the in vitro and in vivo evaluation of the hypoallergenic Der p 1 and Der p 2 derivatives in order to select the best candidates for immunotherapy of mite allergic patients. These vaccines will be tested extensively in animal models to define suitable therapy protocols before first human immunotherapy trials will be conducted.