Epitopes described in "A major allergen gene-fusion protein for potential usage in allergen-specific immunotherapy."

Article Authors:Fatimah Kussebi; Fariba Karamloo; Claudio Rhyner; Peter Schmid-Grendelmeier; Maria Salagianni; Christian Mannhart; Mübeccel Akdis; Lyudmilla Soldatova; Zora Markovic-Housley; Barbara R Von Beust; Thomas Kündig; David M Kemeny; Kurt Blaser; Reto Crameri; Cezmi A Akdis
Article Title:A major allergen gene-fusion protein for potential usage in allergen-specific immunotherapy.
Reference Detail
Reference ID:1013371
Abstract:BACKGROUND: Specific immunotherapy is a common treatment of allergic diseases and could potentially be applied to other immunologic disorders. Despite its use in clinical practice, more defined and safer allergy vaccine preparations are required. Differences between epitopes of IgE that recognize the 3-dimensional structure of allergens and T cells that recognize linear amino acid sequences provide a suitable tool for novel vaccine development for specific immunotherapy. OBJECTIVE: The aim of the study was to delete B-cell epitopes and prevent IgE crosslinking, but to preserve T-cell epitopes by fusion of 2 major allergens of bee venom because of a change in the conformation. METHODS: By genetic engineering, we produced a fusion protein composed of the 2 major bee venom allergens: phospholipase A 2 (Api m 1) and hyaluronidase (Api m 2). RESULTS: The Api m [1/2] fusion protein induced T-cell proliferation and both T H 1-type and T H 2-type cytokine responses. In contrast, IgE reactivity was abolished, and profoundly reduced basophil degranulation and type 1 skin test reactivity was observed. Pretreatment of mice with Api m [1/2] fusion protein significantly suppressed the development of specific IgE as well as other antibody isotypes after immunization with the native allergen. CONCLUSION: The novel fusion protein of 2 major allergens bypasses IgE binding and mast cell/basophil IgE FcepsilonRI crosslinking and protects from IgE development.
Affiliations:Swiss Institute of Allergy and Asthma Research, Davos, Switzerland. fatimah.kussebi@charite.de
Reference Type:Literature
PubMed ID:15696088
Journal:J Allergy Clin Immunol
Journal Volume:115
Article Pages:323-9
Journal ISSN:0091-6749
Article Chemical List:Allergens;Antibodies;Antigens, Plant;Bee Venoms;Cytokines;Epitopes;Immunoglobulin G;Insect Proteins;Recombinant Fusion Proteins;Immunoglobulin E;Phospholipases A;Api m 1 allergen, Apis mellifera;Api m 2 allergen, Apis mellifera;Hyaluronoglucosaminidase
Article MeSH List:Adult; Allergens(genetics; immunology); Animals; Antibodies(analysis; immunology); Antibody Formation(drug effects); Antibody Specificity; Antigens, Plant; Bee Venoms(immunology); Cell Division(drug effects); Cells, Cultured; Cytokines(metabolism); Epitopes; Humans; Hyaluronoglucosaminidase(genetics); Immunoglobulin E(analysis; immunology); Immunoglobulin G(analysis); Immunotherapy; Insect Proteins; Mice; Middle Aged; Phospholipases A(genetics; immunology); Recombinant Fusion Proteins(immunology; pharmacology; therapeutic use); T-Lymphocytes(cytology; metabolism); Vaccination
Curation Last Updated:2015-01-27 20:14:35