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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 |
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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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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.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>EISSN: 1365-2567</identifier><identifier>DOI: 10.4049/jimmunol.179.8.5309</identifier><identifier>PMID: 17911617</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>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</subject><ispartof>Journal of Immunology, 2007-10, Vol.179 (8), p.5309-5316</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-d1debbacacccb853628f1eba8657fe5230926d84cce99862a767a1a8d45c7bf13</citedby><cites>FETCH-LOGICAL-c499t-d1debbacacccb853628f1eba8657fe5230926d84cce99862a767a1a8d45c7bf13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17911617$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:116083079$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Pree, Ines</creatorcontrib><creatorcontrib>Reisinger, Jurgen</creatorcontrib><creatorcontrib>Focke, Margit</creatorcontrib><creatorcontrib>Vrtala, Susanne</creatorcontrib><creatorcontrib>Pauli, Gabrielle</creatorcontrib><creatorcontrib>van Hage, Marianne</creatorcontrib><creatorcontrib>Cromwell, Oliver</creatorcontrib><creatorcontrib>Gadermaier, Elisabeth</creatorcontrib><creatorcontrib>Egger, Cornelia</creatorcontrib><creatorcontrib>Reider, Norbert</creatorcontrib><creatorcontrib>Horak, Friedrich</creatorcontrib><creatorcontrib>Valenta, Rudolf</creatorcontrib><creatorcontrib>Niederberger, Verena</creatorcontrib><title>Analysis of Epitope-Specific Immune Responses Induced by Vaccination with Structurally Folded and Unfolded Recombinant Bet v 1 Allergen Derivatives in Man</title><title>Journal of Immunology</title><addtitle>J Immunol</addtitle><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.</description><subject>Allergens - administration & dosage</subject><subject>Allergens - chemistry</subject><subject>Allergens - genetics</subject><subject>Allergens - immunology</subject><subject>Antibody Specificity</subject><subject>Betula - genetics</subject><subject>Betula - immunology</subject><subject>Double-Blind Method</subject><subject>Epitopes - administration & dosage</subject><subject>Epitopes - genetics</subject><subject>Epitopes - immunology</subject><subject>Humans</subject><subject>Immunoglobulin A - biosynthesis</subject><subject>Immunoglobulin E - biosynthesis</subject><subject>Immunoglobulin G - biosynthesis</subject><subject>Immunoglobulin M - biosynthesis</subject><subject>Intradermal Tests</subject><subject>Medicin och hälsovetenskap</subject><subject>Peptide Fragments - administration & dosage</subject><subject>Peptide Fragments - chemistry</subject><subject>Peptide Fragments - genetics</subject><subject>Peptide Fragments - immunology</subject><subject>Pollen - chemistry</subject><subject>Pollen - genetics</subject><subject>Pollen - immunology</subject><subject>Protein Engineering</subject><subject>Protein Folding</subject><subject>Vaccines, Synthetic - administration & dosage</subject><subject>Vaccines, Synthetic - chemistry</subject><subject>Vaccines, Synthetic - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><issn>1365-2567</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNqFks1u1DAQgC0EosvCEyAhn-CUxc6PYx-X0sJKRUgt5Wo59qTrktjBTjbaV-Fp8Wq3lAvi5B9938x4PAi9pmRVklK8v7d9PznfrWgtVnxVFUQ8QQtaVSRjjLCnaEFInme0ZvUZehHjPSGEkbx8js6SQSmj9QL9WjvV7aON2Lf4YrCjHyC7GUDb1mq8OWQAfA1x8C5CxBtnJg0GN3v8XWltnRqtd3i24xbfjGHS4xRU1-3xpe9M4pQz-Na1x8M1aN83yXEj_gAj3mGK110H4Q4c_gjB7lK0XcpiHf6i3Ev0rFVdhFendYluLy--nX_Orr5-2pyvrzJdCjFmhhpoGqVTObrhVcFy3lJoFGdV3UKVp7bkzPBSaxCCs1ylfiiquCkrXTctLZYoO8aNMwxTI4dgexX20isrT1c_0g5kxWpRFIkX_-SH4M2j9CCmXhNekGQv0dujm8CfE8RR9jZq6DrlwE9RMl6UtOTsvyCta8LSexJYHEEdfIwB2j_1UCIPcyIf5iQ5QnJ5mJNkvTmFn5oezKNzGowEvDsCW3u3nW0AGfv0sQmncp7nv0L9Bp9RzcU</recordid><startdate>20071015</startdate><enddate>20071015</enddate><creator>Pree, Ines</creator><creator>Reisinger, Jurgen</creator><creator>Focke, Margit</creator><creator>Vrtala, Susanne</creator><creator>Pauli, Gabrielle</creator><creator>van Hage, Marianne</creator><creator>Cromwell, Oliver</creator><creator>Gadermaier, Elisabeth</creator><creator>Egger, Cornelia</creator><creator>Reider, Norbert</creator><creator>Horak, Friedrich</creator><creator>Valenta, Rudolf</creator><creator>Niederberger, Verena</creator><general>Am Assoc Immnol</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20071015</creationdate><title>Analysis of Epitope-Specific Immune Responses Induced by Vaccination with Structurally Folded and Unfolded Recombinant Bet v 1 Allergen Derivatives in Man</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-d1debbacacccb853628f1eba8657fe5230926d84cce99862a767a1a8d45c7bf13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Allergens - administration & dosage</topic><topic>Allergens - chemistry</topic><topic>Allergens - genetics</topic><topic>Allergens - immunology</topic><topic>Antibody Specificity</topic><topic>Betula - genetics</topic><topic>Betula - immunology</topic><topic>Double-Blind Method</topic><topic>Epitopes - administration & dosage</topic><topic>Epitopes - genetics</topic><topic>Epitopes - immunology</topic><topic>Humans</topic><topic>Immunoglobulin A - biosynthesis</topic><topic>Immunoglobulin E - biosynthesis</topic><topic>Immunoglobulin G - biosynthesis</topic><topic>Immunoglobulin M - biosynthesis</topic><topic>Intradermal Tests</topic><topic>Medicin och hälsovetenskap</topic><topic>Peptide Fragments - administration & dosage</topic><topic>Peptide Fragments - chemistry</topic><topic>Peptide Fragments - genetics</topic><topic>Peptide Fragments - immunology</topic><topic>Pollen - chemistry</topic><topic>Pollen - genetics</topic><topic>Pollen - immunology</topic><topic>Protein Engineering</topic><topic>Protein Folding</topic><topic>Vaccines, Synthetic - administration & dosage</topic><topic>Vaccines, Synthetic - chemistry</topic><topic>Vaccines, Synthetic - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pree, Ines</creatorcontrib><creatorcontrib>Reisinger, Jurgen</creatorcontrib><creatorcontrib>Focke, Margit</creatorcontrib><creatorcontrib>Vrtala, Susanne</creatorcontrib><creatorcontrib>Pauli, Gabrielle</creatorcontrib><creatorcontrib>van Hage, Marianne</creatorcontrib><creatorcontrib>Cromwell, Oliver</creatorcontrib><creatorcontrib>Gadermaier, Elisabeth</creatorcontrib><creatorcontrib>Egger, Cornelia</creatorcontrib><creatorcontrib>Reider, Norbert</creatorcontrib><creatorcontrib>Horak, Friedrich</creatorcontrib><creatorcontrib>Valenta, Rudolf</creatorcontrib><creatorcontrib>Niederberger, Verena</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Journal of Immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pree, Ines</au><au>Reisinger, Jurgen</au><au>Focke, Margit</au><au>Vrtala, Susanne</au><au>Pauli, Gabrielle</au><au>van Hage, Marianne</au><au>Cromwell, Oliver</au><au>Gadermaier, Elisabeth</au><au>Egger, Cornelia</au><au>Reider, Norbert</au><au>Horak, Friedrich</au><au>Valenta, Rudolf</au><au>Niederberger, Verena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of Epitope-Specific Immune Responses Induced by Vaccination with Structurally Folded and Unfolded Recombinant Bet v 1 Allergen Derivatives in Man</atitle><jtitle>Journal of Immunology</jtitle><addtitle>J Immunol</addtitle><date>2007-10-15</date><risdate>2007</risdate><volume>179</volume><issue>8</issue><spage>5309</spage><epage>5316</epage><pages>5309-5316</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><eissn>1365-2567</eissn><abstract>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.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>17911617</pmid><doi>10.4049/jimmunol.179.8.5309</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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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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