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Analysis of Epitope-Specific Immune Responses Induced by Vaccination with Structurally Folded and Unfolded Recombinant Bet v 1 Allergen Derivatives in Man

Previously, we have constructed recombinant derivatives of the major birch pollen allergen, Bet v 1, with a more than 100-fold reduced ability to induce IgE-mediated allergic reactions. These derivatives differed from each other because the two recombinant Bet v 1 fragments represented unfolded mole...

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Published in:Journal of Immunology 2007-10, Vol.179 (8), p.5309-5316
Main Authors: Pree, Ines, Reisinger, Jurgen, Focke, Margit, Vrtala, Susanne, Pauli, Gabrielle, van Hage, Marianne, Cromwell, Oliver, Gadermaier, Elisabeth, Egger, Cornelia, Reider, Norbert, Horak, Friedrich, Valenta, Rudolf, Niederberger, Verena
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cited_by cdi_FETCH-LOGICAL-c499t-d1debbacacccb853628f1eba8657fe5230926d84cce99862a767a1a8d45c7bf13
cites cdi_FETCH-LOGICAL-c499t-d1debbacacccb853628f1eba8657fe5230926d84cce99862a767a1a8d45c7bf13
container_end_page 5316
container_issue 8
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container_title Journal of Immunology
container_volume 179
creator Pree, Ines
Reisinger, Jurgen
Focke, Margit
Vrtala, Susanne
Pauli, Gabrielle
van Hage, Marianne
Cromwell, Oliver
Gadermaier, Elisabeth
Egger, Cornelia
Reider, Norbert
Horak, Friedrich
Valenta, Rudolf
Niederberger, Verena
description Previously, we have constructed recombinant derivatives of the major birch pollen allergen, Bet v 1, with a more than 100-fold reduced ability to induce IgE-mediated allergic reactions. These derivatives differed from each other because the two recombinant Bet v 1 fragments represented unfolded molecules whereas the recombinant trimer resembled most of the structural fold of the Bet v 1 allergen. In this study, we analyzed the Ab (IgE, IgG subclass, IgA, IgM) response to Bet v 1, recombinant and synthetic Bet v 1-derived peptides in birch pollen allergic patients who had been vaccinated with the derivatives or adjuvant alone. Furthermore, we studied the induction of IgE-mediated skin responses in these patients using Bet v 1 and Bet v 1 fragments. Both types of vaccines induced a comparable IgG1 and IgG4 response against new sequential epitopes which overlap with the conformational IgE epitopes of Bet v 1. This response was 4- to 5-fold higher than that induced by immunotherapy with birch pollen extract. Trimer more than fragments induced also IgE responses against new epitopes and a transient increase in skin sensitivity to the fragments at the beginning of therapy. However, skin reactions to Bet v 1 tended to decrease one year after treatment in both actively treated groups. We demonstrate that vaccination with folded and unfolded recombinant allergen derivatives induces IgG Abs against new epitopes. These data may be important for the development of therapeutic as well as prophylactic vaccines based on recombinant allergens.
doi_str_mv 10.4049/jimmunol.179.8.5309
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source Wiley; Free E-Journal (出版社公開部分のみ); PubMed
subjects Allergens - administration & dosage
Allergens - chemistry
Allergens - genetics
Allergens - immunology
Antibody Specificity
Betula - genetics
Betula - immunology
Double-Blind Method
Epitopes - administration & dosage
Epitopes - genetics
Epitopes - immunology
Humans
Immunoglobulin A - biosynthesis
Immunoglobulin E - biosynthesis
Immunoglobulin G - biosynthesis
Immunoglobulin M - biosynthesis
Intradermal Tests
Medicin och hälsovetenskap
Peptide Fragments - administration & dosage
Peptide Fragments - chemistry
Peptide Fragments - genetics
Peptide Fragments - immunology
Pollen - chemistry
Pollen - genetics
Pollen - immunology
Protein Engineering
Protein Folding
Vaccines, Synthetic - administration & dosage
Vaccines, Synthetic - chemistry
Vaccines, Synthetic - immunology
title Analysis of Epitope-Specific Immune Responses Induced by Vaccination with Structurally Folded and Unfolded Recombinant Bet v 1 Allergen Derivatives in Man
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