HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holm, J. Articles by Spangfort, M. D. Search for Related Content PubMed PubMed Citation Articles by Holm, J. Articles by Spangfort, M. D.

Allergy Vaccine Engineering: Epitope Modulation of Recombinant Bet v 1 Reduces IgE Binding but Retains Protein Folding Pattern for Induction of Protective Blocking-Antibody Responses¹

Jens Holm^2,*,, Michael Gajhede^3,, Mercedes Ferreras^*, Anette Henriksen^4,, Henrik Ipsen^*, Jørgen N. Larsen^*, Lise Lund^*, Henrik Jacobi^*, Anders Millner^*, Peter A. Würtzen^* and Michael D. Spangfort^*

^* Research Department, ALK-Abelló, Hørsholm, Denmark; and Protein Structure Group, Department of Chemistry, University of Copenhagen, Copenhagen, Denmark

Human type 1 immediate allergic response symptoms are caused by mediator release from basophils and mast cells. This event is triggered by allergens aggregating preformed IgE Abs bound to the high-affinity receptor (FcRI) on these cells. Thus, the allergen/IgE interaction is crucial for the cascade leading to the allergic and anaphylactic response. Two genetically engineered forms of the white birch pollen major allergen Bet v 1 with point mutations directed at molecular surfaces have been characterized. Four and nine point mutations led to a significant reduction of the binding to human serum IgE, suggesting a mutation-induced distortion of IgE-binding B cell epitopes. In addition, the mutated allergens showed a decrease in anaphylactic potential, because histamine release from human basophils was significantly reduced. Retained -carbon backbone folding pattern of the mutated allergens was indicated by x-ray diffraction analysis and circular dichroism spectroscopy. The rBet v 1 mutants were able to induce proliferation of T cell lines derived from birch pollen allergic patients. The stimulation indices were similar to the indices of nonmutated rBet v 1 and natural Bet v 1 purified from birch pollen. The ability of anti-rBet v 1 mutant specific mouse IgG serum to block binding of human serum IgE to rBet v 1 demonstrates that the engineered rBet v 1 mutants are able to induce Abs reactive with nonmodified Bet v 1. rBet v 1 mutants may constitute vaccine candidates with improved efficacy/safety profiles for safer allergy vaccination.

This article has been cited by other articles:

				S. L. Chan, T. C. Ong, Y. F. Gao, Y. S. Tiong, D. Y. Wang, F. T. Chew, and Y. K. Mok Nuclear Magnetic Resonance Structure and IgE Epitopes of Blo t 5, a Major Dust Mite Allergen J. Immunol., August 15, 2008; 181(4): 2586 - 2596. [Abstract] [Full Text] [PDF]

				G. Gafvelin, S. Parmley, T. Neimert-Andersson, U. Blank, T. L. J. Eriksson, M. van Hage, and J. Punnonen Hypoallergens for Allergen-specific Immunotherapy by Directed Molecular Evolution of Mite Group 2 Allergens J. Biol. Chem., February 9, 2007; 282(6): 3778 - 3787. [Abstract] [Full Text] [PDF]

				S. L. Chan, S. T. Ong, S. Y. Ong, F. T. Chew, and Y. K. Mok Nuclear magnetic resonance structure-based epitope mapping and modulation of dust mite group 13 allergen as a hypoallergen. J. Immunol., April 15, 2006; 176(8): 4852 - 4860. [Abstract] [Full Text] [PDF]

				G. Reese, J. Viebranz, S. M. Leong-Kee, M. Plante, I. Lauer, S. Randow, M. S.-M. Moncin, R. Ayuso, S. B. Lehrer, and S. Vieths Reduced Allergenic Potency of VR9-1, a Mutant of the Major Shrimp Allergen Pen a 1 (Tropomyosin) J. Immunol., December 15, 2005; 175(12): 8354 - 8364. [Abstract] [Full Text] [PDF]

				K. Meno, P. B. Thorsted, H. Ipsen, O. Kristensen, J. N. Larsen, M. D. Spangfort, M. Gajhede, and K. Lund The Crystal Structure of Recombinant proDer p 1, a Major House Dust Mite Proteolytic Allergen J. Immunol., September 15, 2005; 175(6): 3835 - 3845. [Abstract] [Full Text] [PDF]