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Forschungsdatenbank PMU-SQQUID

Allergy multivaccines created by DNA shuffling of tree pollen allergens.
Wallner, M; Stöcklinger, A; Thalhamer, T; Bohle, B; Vogel, L; Briza, P; Breiteneder, H; Vieths, S; Hartl, A; Mari, A; Ebner, C; Lackner, P; Hammerl, P; Thalhamer, J; Ferreira, F;
J Allergy Clin Immunol. 2007; 120(2):374-380
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Hartl Arnulf Josef

Abstract

Background: The major allergens of trees belonging to the Fagales order are collectively known as the Bet v 1 family. Members of the Fagales order have distinct geographic distribution, and it is expected that depending on the exposure pattern of the individual, inclusion of other Bet v 1 family members might increase the efficacy of the treatment. Objective: We aimed to generate molecules that are suitable for specific immunotherapy not only against birch pollen allergy but also against allergies caused by other cross-reactive tree pollens. Methods: Fourteen genes of the Bet v 1 family were randomly recombined in vitro by means of DNA shuffling. This library of chimeric proteins was screened for molecules displaying low capacity to induce release of inflammatory mediators but with T-cell immunogenicity higher than that of the parental allergens. Results: Two chimeric proteins were selected from the library of shuffled clones displaying low allergenicity and high immunogenicity, as determined in in vitro assays using human and animal cells and antibodies, as well as in vivo in animal models of allergy. Conclusion: Our results show that it is possible to randomly recombine in vitro T- and B-cell epitopes of a family of related allergens and to select chimeric proteins that perfectly match the criteria presently thought to be relevant for improving allergen-specific immunotherapy. Clinical implications: The hypoallergenic chimeras described here recombine epitopes of the major Fagales pollen allergens and thus can efficiently substitute a mixture of extracts used for treating patients with tree pollen-induced spring pollinosis worldwide.


Useful keywords (using NLM MeSH Indexing)

Allergens/genetics*

Amino Acid Sequence

Animals

Antibody Formation

Betula/immunology

Cell Line

DNA Shuffling*

DNA, Plant*

Epitopes

Female

Gene Library

Humans

Hypersensitivity/prevention*

control*

Immunization

Immunoglobulin E/immunology

Mice

Mice, Inbred BALB C

Mice, Inbred C3H

Molecular Sequence Data

Molecular Weight

Monocytes/immunology

Pollen/immunology*

Rats

Recombinant Fusion Proteins/chemistry

Recombinant Fusion Proteins/genetics

Recombinant Fusion Proteins/immunology

T-Lymphocytes/immunology

Trees/immunology*

Vaccines, Combined/chemical synthesis*


Find related publications in this database (Keywords)

gene shuffling
tree pollen allergens
Bet v 1 family
T-cell epitope
IgE epitope
IgE cross-reactivity
genetic immunization
hypoallergen
allergen chimera