Reduction of the in vivo allergenicity of Der p 2, the major house-dust mite allergen, by genetic engineering

Kuan Wei Chen, Gudrun Fuchs, Karoline Sonneck, Anna Gieras, Ines Swoboda, Nikolas Douladiris, Birgit Linhart, Marija Jankovic, Tea Pavkov, Walter Keller, Nikolaos G. Papadopoulos, Peter Valent, Rudolf Valenta, Susanne Vrtala

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The major allergen of the house-dust mite Dermatophagoides pteronyssinus, Der p 2, is recognized by approximately 90% of mite-allergic patients. We have produced two recombinant fragments of Der p 2 comprising aa 1-53 and aa 54-129 and a hybrid molecule (aa 54-129 + 1-53), combining the two fragments in inverse order, by genetic engineering. The recombinant Der p 2 derivatives were expressed in E. coli and purified to homogeneity. rDer p 2 derivatives (fragments and hybrid) showed a considerably reduced beta sheet structure and IgE reactivity compared to the Der p 2 wild-type allergen. The allergenic activity of the Der p 2 derivatives was reduced more than tenfold as evaluated in vitro in basophil activation assays and in vivo by skin prick testing of mite-allergic patients. Immunization of mice and rabbits with rDer p 2 derivatives induced Der p 2-specific IgG antibodies, which inhibited the binding of allergic patients' IgE to Der p 2. Immunization of mice with rDer p 2 derivatives induced less allergenic IgE responses than immunization with rDer p 2. Thus the rDer p 2 derivatives exhibited less in vivo allergenic activity and allergenicity than the Der p 2 allergen but preserved immunogenicity and may hence represent candidates for specific immunotherapy of house-dust mite allergy. © 2008 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)2486-2498
    Number of pages12
    JournalMolecular immunology
    Volume45
    Issue number9
    DOIs
    Publication statusPublished - May 2008

    Keywords

    • Der p 2
    • Genetic engineering
    • House-dust mite allergy
    • Hypoallergenic allergen derivatives
    • Immunotherapy

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