Hypoallergenic derivatives of the major birch pollen allergen Bet v 1 obtained by rational sequence reassembly - 07/08/11
Reprint requests: Rudolf Valenta, MD, Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, AKH 3Q, Waehringer Guertel 18-20 A-1090 Vienna, Austria.Abstract |
Background |
At least 100 million patients suffer from birch pollen allergy.
Objective |
Rational design of recombinant derivatives of the major birch pollen allergen, Bet v 1, characterized by reduced IgE reactivity, preservation of sequences relevant for the induction of allergen-specific blocking IgG, and maintenance of T-cell epitopes for immunotherapy of birch pollen allergy.
Methods |
Three recombinant mosaic proteins derived from Bet v 1 were generated by reassembly of codon-optimized genes coding for Bet v 1 fragments containing the elements for the induction of allergen-specific blocking IgG antibodies and the major T-cell epitopes. The proteins were expressed in Escherichia coli as recombinant mosaic molecules and compared with the Bet v 1 wild-type protein by chemical and structural methods, regarding IgE-binding and IgG-binding capacity, in basophil activation assays and tested for the in vivo induction of IgG responses.
Results |
Three recombinant Bet v 1 (rBet v 1) mosaic proteins with strongly reduced IgE reactivity and allergenic activity were expressed and purified. Immunization with the recombinant hypoallergens induced IgG antibodies that inhibited IgE reactivity of patients with allergy to Bet v 1 comparable to those induced with the rBet v 1 wild-type allergen.
Conclusion |
We report the generation and preclinical characterization of 3 hypoallergenic rBet v 1 derivatives with suitable properties for immunotherapy of birch pollen allergy.
Le texte complet de cet article est disponible en PDF.Key words : Birch pollen allergy, immunotherapy, rBet v 1, recombinant hypoallergenic derivative molecules
Abbreviations used : HSA, PBS-T, rBet v 1
Plan
| Supported by grants F1803, F1804, F1815, F1809, and L214-B13 of the Austrian Science Fund (FWF) and by a research grant from Biomay, Vienna, Austria. |
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| Disclosure of potential conflict of interest: R. Valenta receives research support from the Austrian Science Fund, the Christian Doppler Research Association, Biomay, and Phadia and has provided legal consultation services/expert witness testimony in cases related to allergy diagnostics and allergy therapeutics. D. Zafred receives research support from the Austrian Science Fund. W. Keller receives research support from the Austrian Science Fund. The rest of the authors have declared that they have no conflict of interest. |
Vol 126 - N° 5
P. 1024 - novembre 2010 Retour au numéro
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