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Genetic engineering of trimers of hypoallergenic fragments of the major birch pollen allergen, Bet v 1, for allergy vaccination
Abstract An immunotherapy trial performed in allergic patients with hypoallergenic recombinant fragments, comprising aa 1–74 and 75–160 of the major birch pollen allergen, Bet v 1, has indicated that the induction of allergen-specific IgG responses may be an important mechanism of this treatment. To...
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Published in: | Vaccine 2011-03, Vol.29 (11), p.2140-2148 |
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description | Abstract An immunotherapy trial performed in allergic patients with hypoallergenic recombinant fragments, comprising aa 1–74 and 75–160 of the major birch pollen allergen, Bet v 1, has indicated that the induction of allergen-specific IgG responses may be an important mechanism of this treatment. To investigate whether the immunogenicity of the rBet v 1 fragments can be increased, recombinant trimers of the fragments were produced. For this purpose, DNA trimers of rBet v 1 aa 1–74 as well as of rBet v 1 aa 75–160 were subcloned into expression plasmid pET 17b, expressed in Escherichia coli and purified. The fragments as well as the fragment trimers showed a reduced IgE-binding capacity and allergenic activity compared to rBet v 1 wildtype when tested in allergic patients. Both rBet v 1 aa 75–160 monomer and trimer induced high titers of allergen-specific IgG1 Abs in mice. Interestingly, rBet v 1 aa 1–74 trimer induced a much higher IgG1 response to rBet v 1 than rBet v 1 aa 1–74 monomer. Consequently, IgG Abs induced with the rBet v 1 aa 1–74 trimer inhibited birch pollen allergic patients’ IgE-binding 10-fold more efficiently than IgG Abs induced with the monomer. Our data show that the immunogenicity of allergy vaccines can be increased by oligomerization. |
doi_str_mv | 10.1016/j.vaccine.2010.12.080 |
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To investigate whether the immunogenicity of the rBet v 1 fragments can be increased, recombinant trimers of the fragments were produced. For this purpose, DNA trimers of rBet v 1 aa 1–74 as well as of rBet v 1 aa 75–160 were subcloned into expression plasmid pET 17b, expressed in Escherichia coli and purified. The fragments as well as the fragment trimers showed a reduced IgE-binding capacity and allergenic activity compared to rBet v 1 wildtype when tested in allergic patients. Both rBet v 1 aa 75–160 monomer and trimer induced high titers of allergen-specific IgG1 Abs in mice. Interestingly, rBet v 1 aa 1–74 trimer induced a much higher IgG1 response to rBet v 1 than rBet v 1 aa 1–74 monomer. Consequently, IgG Abs induced with the rBet v 1 aa 1–74 trimer inhibited birch pollen allergic patients’ IgE-binding 10-fold more efficiently than IgG Abs induced with the monomer. Our data show that the immunogenicity of allergy vaccines can be increased by oligomerization.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2010.12.080</identifier><identifier>PMID: 21215346</identifier><identifier>CODEN: VACCDE</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Allergens ; Allergens - genetics ; Allergens - immunology ; Allergies ; Allergy ; Allergy and Immunology ; Animals ; Antibody Formation ; Antibody Specificity ; Antigens, Plant - genetics ; Antigens, Plant - immunology ; Applied microbiology ; Bet v 1 antigen ; Betula - immunology ; Biological and medical sciences ; Clinical trials ; Cloning, Molecular ; Data processing ; Deoxyribonucleic acid ; Derivatives ; Desensitization, Immunologic ; DNA ; E coli ; Escherichia coli ; Escherichia coli - genetics ; Escherichia coli - metabolism ; Female ; Fundamental and applied biological sciences. Psychology ; Genetic Engineering ; Humans ; Hypersensitivity ; Immunization ; Immunogenicity ; Immunoglobulin E ; Immunoglobulin E - blood ; Immunoglobulin E - immunology ; Immunoglobulin G ; Immunoglobulin G - blood ; Immunoglobulin G - immunology ; Immunotherapy ; Mice ; Mice, Inbred BALB C ; Microbiology ; Monomers ; Oligomerization ; Patients ; Plasmids ; Pollen ; Pollen - immunology ; Recombinant Proteins - genetics ; Recombinant Proteins - immunology ; Rhinitis, Allergic, Seasonal - immunology ; Rhinitis, Allergic, Seasonal - therapy ; Studies ; Vaccines ; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</subject><ispartof>Vaccine, 2011-03, Vol.29 (11), p.2140-2148</ispartof><rights>Elsevier Ltd</rights><rights>2011 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Mar 3, 2011</rights><rights>2011 Elsevier Ltd. All rights reserved. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c677t-ee7d684c62549a60e5c3afd13cc57f2ee8036b514f56417009bc3f1d5b646e013</citedby><cites>FETCH-LOGICAL-c677t-ee7d684c62549a60e5c3afd13cc57f2ee8036b514f56417009bc3f1d5b646e013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23922909$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21215346$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vrtala, Susanne</creatorcontrib><creatorcontrib>Fohr, Monika</creatorcontrib><creatorcontrib>Campana, Raffaela</creatorcontrib><creatorcontrib>Baumgartner, Christian</creatorcontrib><creatorcontrib>Valent, Peter</creatorcontrib><creatorcontrib>Valenta, Rudolf</creatorcontrib><title>Genetic engineering of trimers of hypoallergenic fragments of the major birch pollen allergen, Bet v 1, for allergy vaccination</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract An immunotherapy trial performed in allergic patients with hypoallergenic recombinant fragments, comprising aa 1–74 and 75–160 of the major birch pollen allergen, Bet v 1, has indicated that the induction of allergen-specific IgG responses may be an important mechanism of this treatment. To investigate whether the immunogenicity of the rBet v 1 fragments can be increased, recombinant trimers of the fragments were produced. For this purpose, DNA trimers of rBet v 1 aa 1–74 as well as of rBet v 1 aa 75–160 were subcloned into expression plasmid pET 17b, expressed in Escherichia coli and purified. The fragments as well as the fragment trimers showed a reduced IgE-binding capacity and allergenic activity compared to rBet v 1 wildtype when tested in allergic patients. Both rBet v 1 aa 75–160 monomer and trimer induced high titers of allergen-specific IgG1 Abs in mice. Interestingly, rBet v 1 aa 1–74 trimer induced a much higher IgG1 response to rBet v 1 than rBet v 1 aa 1–74 monomer. Consequently, IgG Abs induced with the rBet v 1 aa 1–74 trimer inhibited birch pollen allergic patients’ IgE-binding 10-fold more efficiently than IgG Abs induced with the monomer. Our data show that the immunogenicity of allergy vaccines can be increased by oligomerization.</description><subject>Allergens</subject><subject>Allergens - genetics</subject><subject>Allergens - immunology</subject><subject>Allergies</subject><subject>Allergy</subject><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Antibody Formation</subject><subject>Antibody Specificity</subject><subject>Antigens, Plant - genetics</subject><subject>Antigens, Plant - immunology</subject><subject>Applied microbiology</subject><subject>Bet v 1 antigen</subject><subject>Betula - immunology</subject><subject>Biological and medical sciences</subject><subject>Clinical trials</subject><subject>Cloning, Molecular</subject><subject>Data processing</subject><subject>Deoxyribonucleic acid</subject><subject>Derivatives</subject><subject>Desensitization, Immunologic</subject><subject>DNA</subject><subject>E coli</subject><subject>Escherichia coli</subject><subject>Escherichia coli - genetics</subject><subject>Escherichia coli - metabolism</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. 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Fohr, Monika ; Campana, Raffaela ; Baumgartner, Christian ; Valent, Peter ; Valenta, Rudolf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c677t-ee7d684c62549a60e5c3afd13cc57f2ee8036b514f56417009bc3f1d5b646e013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Allergens</topic><topic>Allergens - genetics</topic><topic>Allergens - immunology</topic><topic>Allergies</topic><topic>Allergy</topic><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Antibody Formation</topic><topic>Antibody Specificity</topic><topic>Antigens, Plant - genetics</topic><topic>Antigens, Plant - immunology</topic><topic>Applied microbiology</topic><topic>Bet v 1 antigen</topic><topic>Betula - immunology</topic><topic>Biological and medical sciences</topic><topic>Clinical trials</topic><topic>Cloning, Molecular</topic><topic>Data processing</topic><topic>Deoxyribonucleic acid</topic><topic>Derivatives</topic><topic>Desensitization, Immunologic</topic><topic>DNA</topic><topic>E coli</topic><topic>Escherichia coli</topic><topic>Escherichia coli - genetics</topic><topic>Escherichia coli - metabolism</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. 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To investigate whether the immunogenicity of the rBet v 1 fragments can be increased, recombinant trimers of the fragments were produced. For this purpose, DNA trimers of rBet v 1 aa 1–74 as well as of rBet v 1 aa 75–160 were subcloned into expression plasmid pET 17b, expressed in Escherichia coli and purified. The fragments as well as the fragment trimers showed a reduced IgE-binding capacity and allergenic activity compared to rBet v 1 wildtype when tested in allergic patients. Both rBet v 1 aa 75–160 monomer and trimer induced high titers of allergen-specific IgG1 Abs in mice. Interestingly, rBet v 1 aa 1–74 trimer induced a much higher IgG1 response to rBet v 1 than rBet v 1 aa 1–74 monomer. Consequently, IgG Abs induced with the rBet v 1 aa 1–74 trimer inhibited birch pollen allergic patients’ IgE-binding 10-fold more efficiently than IgG Abs induced with the monomer. Our data show that the immunogenicity of allergy vaccines can be increased by oligomerization.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>21215346</pmid><doi>10.1016/j.vaccine.2010.12.080</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Allergens Allergens - genetics Allergens - immunology Allergies Allergy Allergy and Immunology Animals Antibody Formation Antibody Specificity Antigens, Plant - genetics Antigens, Plant - immunology Applied microbiology Bet v 1 antigen Betula - immunology Biological and medical sciences Clinical trials Cloning, Molecular Data processing Deoxyribonucleic acid Derivatives Desensitization, Immunologic DNA E coli Escherichia coli Escherichia coli - genetics Escherichia coli - metabolism Female Fundamental and applied biological sciences. Psychology Genetic Engineering Humans Hypersensitivity Immunization Immunogenicity Immunoglobulin E Immunoglobulin E - blood Immunoglobulin E - immunology Immunoglobulin G Immunoglobulin G - blood Immunoglobulin G - immunology Immunotherapy Mice Mice, Inbred BALB C Microbiology Monomers Oligomerization Patients Plasmids Pollen Pollen - immunology Recombinant Proteins - genetics Recombinant Proteins - immunology Rhinitis, Allergic, Seasonal - immunology Rhinitis, Allergic, Seasonal - therapy Studies Vaccines Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) |
title | Genetic engineering of trimers of hypoallergenic fragments of the major birch pollen allergen, Bet v 1, for allergy vaccination |
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