Epitopes described in "Characterization of a hypoallergenic recombinant Bet v 1 variant as a candidate for allergen-specific immunotherapy."

Article Authors:H Kahlert; R Suck; B Weber; A Nandy; M Wald; W Keller; O Cromwell; H Fiebig
Article Title:Characterization of a hypoallergenic recombinant Bet v 1 variant as a candidate for allergen-specific immunotherapy.
Reference Detail
Reference ID:1012670
Abstract:BACKGROUND: Recombinant allergens and especially their hypoallergenic variants are promising candidates for a more effective and safer specific immunotherapy. METHODS: Physicochemical and immunological characteristics of a folding variant of recombinant Bet v 1 (rBet v 1-FV) were investigated in comparison to natural Bet v 1 (nBet v 1) and the correctly folded recombinant Bet v 1 (rBet v 1-WT) by SDS-PAGE, size exclusion chromatography, multi-angle light scattering, circular dichroism, immunoblotting and enzyme allergosorbent test inhibition assay for detection of IgE reactivity and ELISA with Bet v 1-specific monoclonal antibodies. The functional IgE reactivity of the different Bet v 1 proteins was investigated using basophil activation in terms of CD203c expression and histamine release. T cell reactivity was investigated using T cell lines raised from birch pollen-allergic subjects against nBet v 1. Immunogenicity was investigated in mice. RESULTS: Physicochemical characterization revealed purity, homogeneity and monomeric properties of rBet v 1-FV. Unlike nBet v 1 and rBet v 1-WT, rBet v 1-FV showed almost no IgE binding in immunoblots. The reduction of allergenicity was further proved by IgE-binding inhibition assays, basophil activation and histamine release. T cell reactivity was completely conserved, as demonstrated by proliferation of Bet v 1-specific T cell lines with multiple epitope specificities. rBet v 1-FV showed strong immunogenicity in mice. CONCLUSIONS: Due to its reduced IgE reactivity and decreased capacity to activate basophils, but retained T cell reactivity and strong immunogenicity, rBet v 1-FV proved to be a very promising candidate for specific immunotherapy in birch pollen-allergic subjects.
Affiliations:Allergopharma Joachim Ganzer KG, Reinbek, Germany. helga.kahlert@allergopharma.de
Reference Type:Literature
PubMed ID:17912007
Journal:Int Arch Allergy Immunol
Journal Volume:145
Article Pages:193-206
Journal ISSN:1423-0097
Article Chemical List:Allergens;Epitopes;Immune Sera;Recombinant Proteins;Immunoglobulin E
Article MeSH List:Adolescent; Adult; Aged; Allergens(immunology; metabolism; therapeutic use ); Animals; Antibody Specificity; Basophils(immunology ); Betula(immunology ); Desensitization, Immunologic(methods ); Drug Evaluation, Preclinical; Epitopes(immunology ); Female; Humans; Immune Sera(immunology ); Immunoglobulin E(immunology ); Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Middle Aged; Pollen(immunology ); Protein Folding; Recombinant Proteins(immunology; metabolism; therapeutic use ); Rhinitis, Allergic, Seasonal(immunology; therapy ); T-Lymphocytes(immunology )
Curation Last Updated:2015-01-27 20:10:05