title: Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes.
abstract: Novel approaches for the prevention of allergy are required, because of the inevitably increasing prevalence of allergic diseases during the last 30 years. Here, a recombinant chimeric protein, which comprises the whole amino acid sequences of three bee venom major allergens has been engineered and used in prevention of bee venom sensitization in mice. Phospholipase A2 (Api m 1), hyaluronidase (Api m 2) and melittin (Api m 3) fragments with overlapping amino acids were assembled in a different order in the Api m (1/2/3) chimeric protein, which preserved entire T cell epitopes, whereas B cell epitopes of all three allergens were abrogated. Accordingly, IgE cross-linking leading to mast cell and basophil mediator release was profoundly reduced in humans. Supporting these findings, the Api m (1/2/3) induced 100 to 1000 times less type-1 skin test reactivity in allergic patients. Treatment of mice with Api m (1/2/3) led to a significant reduction of specific IgE development towards native allergen, representing a protective vaccine effect in vivo. These results demonstrate a novel prototype of a preventive allergy vaccine, which preserves the entire T cell epitope repertoire, but bypasses induction of IgE against native allergen, and side effects related to mast cell/basophil IgE FcepsilonRI cross-linking in sensitized individuals.
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland. karamlooflory@compuserve.de
authors.forename: Fariba
authors.initials: F
authors.lastname: Karamloo
authors.forename: Peter
authors.initials: P
authors.lastname: Schmid-Grendelmeier
authors.forename: Fatimah
authors.initials: F
authors.lastname: Kussebi
authors.forename: Mübeccel
authors.initials: M
authors.lastname: Akdis
authors.forename: Maria
authors.initials: M
authors.lastname: Salagianni
authors.forename: Barbara R
authors.initials: BR
authors.lastname: von Beust
authors.forename: Andrea
authors.initials: A
authors.lastname: Reimers
authors.forename: Judith
authors.initials: J
authors.lastname: Zumkehr
authors.forename: Lyudmilla
authors.initials: L
authors.lastname: Soldatova
authors.forename: Zora
authors.initials: Z
authors.lastname: Housley-Markovic
authors.forename: Ulrich
authors.initials: U
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Kündig
authors.forename: David M
authors.initials: DM
authors.lastname: Kemeny
authors.forename: Michael D
authors.initials: MD
authors.lastname: Spangfort
authors.forename: Kurt
authors.initials: K
authors.lastname: Blaser
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D000818:Animals; D052179:Antigens, Plant; D001516:Bees; D001666:Binding Sites, Antibody; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000378:metabolism*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007299:Insect Bites and Stings / Q000276:immunology* / Q000628:therapy; D019476:Insect Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D010741:Phospholipases A / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D054467:Phospholipases A2; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D019476:Insect Proteins; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E; D010741:Phospholipases A; C497838:Api m 1 allergen, Apis mellifera; D054467:Phospholipases A2; C497839:Api m 2 allergen, Apis mellifera; D006821:Hyaluronoglucosaminidase