|
| 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 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 |
|---|
| Date: | 2008 |
|---|
| 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: | 2013-04-25 20:05:42 |
|---|
