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Carrier-bound nonallergenic Der p 2 peptides induce IgG antibodies blocking allergen-induced basophil activation in allergic patients

Authors

  • K.-W. Chen,

    1. Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
    2. Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
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  • M. Focke-Tejkl,

    1. Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
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  • K. Blatt,

    1. Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
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  • M. Kneidinger,

    1. Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
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  • A. Gieras,

    1. Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
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  • F. Dall'Antonia,

    1. Division of Structural Biology, Institute of Molecular Biosciences, Karl-Franzens-University, Graz, Austria
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  • I. Faé,

    1. Department of Blood Group Serology, Medical University of Vienna, Vienna
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  • G. Fischer,

    1. Department of Blood Group Serology, Medical University of Vienna, Vienna
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  • W. Keller,

    1. Division of Structural Biology, Institute of Molecular Biosciences, Karl-Franzens-University, Graz, Austria
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  • P. Valent,

    1. Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
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  • R. Valenta,

    1. Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
    2. Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
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  • S. Vrtala

    Corresponding author
    • Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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  • Edited by: Sarbjit Saini

Correspondence

Susanne Vrtala, Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Tel.: +43 1 40400 5132

Fax: +43 1 40400 5130

E-mail: susanne.vrtala@meduniwien.ac.at

Abstract

Background

More than 90% of house dust mite-allergic patients are sensitized to the major Dermatophagoides pteronyssinus allergen, Der p 2. The aim of this study was to develop and characterize an allergy vaccine based on carrier-bound Der p 2 peptides, which should allow reducing IgE- and T-cell-mediated side-effects during specific immunotherapy (SIT).

Methods

Five Der p 2 peptides (P1–P5) were synthesized and analyzed regarding IgE reactivity and allergenic activity. Lymphoproliferative and cytokine responses induced with Der p 2 and Der p 2 peptides were determined in peripheral blood mononuclear cells from mite-allergic patients. Der p 2-specific IgG antibodies induced with carrier-bound Der p 2 peptides in mice and rabbits were tested for their capacity to inhibit IgE binding and basophil activation in allergic patients.

Results

Of five overlapping peptides (P1–P5) covering the Der p 2 sequence, two peptides (P2 and P4) were identified, which showed no relevant IgE reactivity, allergenic activity, and induced lower Der p 2-specific T-cell activation than Der p 2. However, when coupled to a carrier, P2 and P4 induced Der p 2-specific IgG antibodies in animals, which inhibited allergic patients' IgE binding to the allergen and allergen-induced basophil activation similar as antibodies induced with Der p 2.

Conclusions

Carrier-bound Der p 2 peptides should allow avoiding IgE-mediated side-effects, and because of their low potential to activate allergen-specific T cells, they may reduce late-phase side-effects during SIT. Further, these peptides may be also useful for prophylactic vaccination.

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