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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
Main Authors: Vrtala, Susanne, Fohr, Monika, Campana, Raffaela, Baumgartner, Christian, Valent, Peter, Valenta, Rudolf
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cited_by cdi_FETCH-LOGICAL-c677t-ee7d684c62549a60e5c3afd13cc57f2ee8036b514f56417009bc3f1d5b646e013
cites cdi_FETCH-LOGICAL-c677t-ee7d684c62549a60e5c3afd13cc57f2ee8036b514f56417009bc3f1d5b646e013
container_end_page 2148
container_issue 11
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container_title Vaccine
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creator Vrtala, Susanne
Fohr, Monika
Campana, Raffaela
Baumgartner, Christian
Valent, Peter
Valenta, Rudolf
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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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. 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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. 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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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