Comparison of genetically engineered hypoallergenic rBet v 1 derivatives with rBet v 1 wild-type by skin prick and intradermal testing: results obtained in a French population

Authors

  • Pauli,

    1. 0 Service de Pneumologie and INSERM U-425, Hôpitaux Universitaires de Strasbourg, France, *1 Department of General and Experimental Pathology, Vienna General Hospital, University of Vienna, 2 Department of Otorhinolaryngology, Vienna General Hospital, University of Vienna, Vienna, Austria
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  • Purohit,

    1. 0 Service de Pneumologie and INSERM U-425, Hôpitaux Universitaires de Strasbourg, France, *1 Department of General and Experimental Pathology, Vienna General Hospital, University of Vienna, 2 Department of Otorhinolaryngology, Vienna General Hospital, University of Vienna, Vienna, Austria
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  • Oster,

    1. 0 Service de Pneumologie and INSERM U-425, Hôpitaux Universitaires de Strasbourg, France, *1 Department of General and Experimental Pathology, Vienna General Hospital, University of Vienna, 2 Department of Otorhinolaryngology, Vienna General Hospital, University of Vienna, Vienna, Austria
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  • De Blay,

    1. 0 Service de Pneumologie and INSERM U-425, Hôpitaux Universitaires de Strasbourg, France, *1 Department of General and Experimental Pathology, Vienna General Hospital, University of Vienna, 2 Department of Otorhinolaryngology, Vienna General Hospital, University of Vienna, Vienna, Austria
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  • Vrtala,

    1. 0 Service de Pneumologie and INSERM U-425, Hôpitaux Universitaires de Strasbourg, France, *1 Department of General and Experimental Pathology, Vienna General Hospital, University of Vienna, 2 Department of Otorhinolaryngology, Vienna General Hospital, University of Vienna, Vienna, Austria
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  • * Niederberger,

    1. 0 Service de Pneumologie and INSERM U-425, Hôpitaux Universitaires de Strasbourg, France, *1 Department of General and Experimental Pathology, Vienna General Hospital, University of Vienna, 2 Department of Otorhinolaryngology, Vienna General Hospital, University of Vienna, Vienna, Austria
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  • Kraft,

    1. 0 Service de Pneumologie and INSERM U-425, Hôpitaux Universitaires de Strasbourg, France, *1 Department of General and Experimental Pathology, Vienna General Hospital, University of Vienna, 2 Department of Otorhinolaryngology, Vienna General Hospital, University of Vienna, Vienna, Austria
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  • and * Valenta *

    1. 0 Service de Pneumologie and INSERM U-425, Hôpitaux Universitaires de Strasbourg, France, *1 Department of General and Experimental Pathology, Vienna General Hospital, University of Vienna, 2 Department of Otorhinolaryngology, Vienna General Hospital, University of Vienna, Vienna, Austria
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Pauli Service de Pneumologie, Hôpitaux Universitaires de Strasbourg, BP 426, 67091 Strasbourg Cedex, France.

Abstract

Background

Bet v 1, the major allergen in birch pollen, is recognized by more than 90% of patients allergic to birch in northern and central Europe. Immunotherapy is commonly performed with birch pollen extracts. Recently, hypoallergenic derivatives of Bet v 1 (rBet v 1 fragments, rBet v 1 dimer and trimer) were constructed and purified.

Objective

Our aim was to compare the allergenic activity of wild-type rBet v 1 with recombinant Bet v 1 derivatives (rBet v 1 fragments, dimer and trimer) with potentially reduced anaphylactic activity by skin testing in a French population.

Methods

Among the 36 birch pollen allergic patients included in the study, 29 were tested by skin prick testing and 30 by intradermal injections with purified monosubstances: rBet v 1 fragments (F1: aa1–74 and F2: aa75–160), Bet v 1 dimer and trimer. Intradermal tests were performed by the end-point intradermal titration method. Eight of the intradermally-tested patients were previously hyposensitized. Tests were performed over a period of 6 months (before, during and after birch pollen season); Bet v 1-specific IgE and IgG4 subclass responses were measured by immunoblotting and ELISA.

Results

All patients showed lower reactivity with the modified rBet v 1 allergens, both in skin prick and intradermal tests. In 25 and 23 out of 29 patients the lowest concentration of fragment 1 and 2, respectively, resulting in a positive prick test was 100-fold higher than the lowest concentration of monomer resulting in a positive prick test. For dimer it was 100-fold or more in 25 out of 29 patients, and for trimer it was 100-fold or superior in 26 out of 29 patients. By intradermal testing, the end-point concentration was 160-fold higher for trimer than for monomer in 24 patients and 40-fold higher in five patients. For the two fragments the end-point concentration was 160-fold higher in 20 out of 22 patients.

Conclusion

Genetically modified hypoallergenic derivatives of the major birch pollen allergen, Bet v 1 showed reduced capacity to induce immediate type skin reactions. They may represent candidate molecules for immunotherapy of birch pollen allergy with reduced risk of anaphylactic side-effects.

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