title: A major allergen gene-fusion protein for potential usage in allergen-specific immunotherapy.
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.
  
  
  CONCLUSIONS
  The novel fusion protein of 2 major allergens bypasses IgE binding and mast cell/basophil IgE FcepsilonRI crosslinking and protects from IgE development.
authors.affiliation: Swiss Institute of Allergy and Asthma Research, Davos, Switzerland. fatimah.kussebi@charite.de
authors.forename: Fatimah
authors.initials: F
authors.lastname: Kussebi
authors.forename: Fariba
authors.initials: F
authors.lastname: Karamloo
authors.forename: Claudio
authors.initials: C
authors.lastname: Rhyner
authors.forename: Peter
authors.initials: P
authors.lastname: Schmid-Grendelmeier
authors.forename: Maria
authors.initials: M
authors.lastname: Salagianni
authors.forename: Christian
authors.initials: C
authors.lastname: Mannhart
authors.forename: Mübeccel
authors.initials: M
authors.lastname: Akdis
authors.forename: Lyudmilla
authors.initials: L
authors.lastname: Soldatova
authors.forename: Zora
authors.initials: Z
authors.lastname: Markovic-Housley
authors.forename: Barbara R
authors.initials: BR
authors.lastname: Von Beust
authors.forename: Thomas
authors.initials: T
authors.lastname: Kündig
authors.forename: David M
authors.initials: DM
authors.lastname: Kemeny
authors.forename: Kurt
authors.initials: K
authors.lastname: Blaser
authors.forename: Reto
authors.initials: R
authors.lastname: Crameri
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
mesh_terms: D000328:Adult; D000485:Allergens / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects; D000918:Antibody Specificity; D052179:Antigens, Plant; D001514:Bee Venoms / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000235:genetics*; D007073:Immunoglobulin E / Q000032:analysis / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis; D007167:Immunotherapy; D019476:Insect Proteins; D051379:Mice; D008875:Middle Aged; D010741:Phospholipases A / Q000235:genetics* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D014611:Vaccination
chemical_list: D000485:Allergens; D000906:Antibodies; D052179:Antigens, Plant; D001514:Bee Venoms; D016207:Cytokines; D000939:Epitopes; D007074:Immunoglobulin G; D019476:Insect Proteins; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E; D010741:Phospholipases A; C497838:Api m 1 allergen, Apis mellifera; C497839:Api m 2 allergen, Apis mellifera; D006821:Hyaluronoglucosaminidase