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Clinical & Experimental Allergy

Carrier-bound Alt a 1 peptides without allergenic activity for vaccination against Alternaria alternata allergy

Authors

  • T. E. Twaroch,

    1. Christian Doppler Laboratory for Allergy Research, 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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  • M. Focke,

    1. Christian Doppler Laboratory for Allergy Research, 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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  • K. Fleischmann,

    1. Christian Doppler Laboratory for Allergy Research, 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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  • N. Balic,

    1. Clinical Institute for Medical and Chemical Laboratory Diagnostics
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  • C. Lupinek,

    1. Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Vienna, Austria
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  • K. Blatt,

    1. 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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  • R. Ferrara,

    1. Center for Molecular Allergology, IDI-IRCCS, Rome, Italy
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  • A. Mari,

    1. Center for Molecular Allergology, IDI-IRCCS, Rome, Italy
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  • C. Ebner,

    1. Allergy Clinic Reumannplatz, Vienna, Austria
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  • P. Valent,

    1. 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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  • S. Spitzauer,

    1. Clinical Institute for Medical and Chemical Laboratory Diagnostics
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  • I. Swoboda,

    1. Christian Doppler Laboratory for Allergy Research, 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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  • R. Valenta

    1. Christian Doppler Laboratory for Allergy Research, 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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Correspondence:

Rudolf Valenta, Christian Doppler Laboratory for Allergy Research, 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. E-mail: rudolf.valenta@meduniwien.ac.at

Abstract

Background

The mould Alternaria alternata is a major elicitor of allergic asthma. Diagnosis and specific immunotherapy (SIT) of Alternaria allergy are often limited by the insufficient quality of natural mould extracts.

Objective

To investigate whether recombinant Alt a 1 can be used for reliable diagnosis of Alternaria alternata allergy and to develop a safe, non-allergenic vaccine for SIT of Alternaria allergy.

Methods

The qualitative sensitization profile of 80 Alternaria-allergic patients from Austria and Italy was investigated using an allergen micro-array and the amount of Alternaria-specific IgE directed to rAlt a 1 was quantified by ImmunoCAP measurements. Peptides spanning regions of predicted high surface accessibility of Alt a 1 were synthesized and tested for IgE reactivity and allergenic activity, using sera and basophils from allergic patients. Carrier-bound peptides were studied for their ability to induce IgG antibodies in rabbits which recognize Alt a 1 and inhibit allergic patients’ IgE reactivity to Alt a 1.

Results

rAlt a 1 allowed diagnosis of Alternaria allergy in all tested patients, bound the vast majority (i.e. >95%) of Alternaria-specific IgE and elicited basophil activation already at a concentration of 0.1 ng/mL. Four non-allergenic peptides were synthesized which, after coupling to the carrier protein keyhole limpet hemocyanin, induced Alt a 1-specific IgG and inhibited allergic patients’ IgE binding to Alt a 1.

Conclusions and clinical relevance

rAlt a 1 is a highly allergenic molecule allowing sensitive diagnosis of Alternaria allergy. Carrier-bound non-allergenic Alt a 1 peptides are candidates for safe SIT of Alternaria allergy.

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