Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes.
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.
Karamloo
Fariba
F
Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland. karamlooflory@compuserve.de
Schmid-Grendelmeier
Peter
P
Kussebi
Fatimah
F
Akdis
Mübeccel
M
Salagianni
Maria
M
von Beust
Barbara R
BR
Reimers
Andrea
A
Zumkehr
Judith
J
Soldatova
Lyudmilla
L
Housley-Markovic
Zora
Z
Müller
Ulrich
U
Kündig
Thomas
T
Kemeny
David M
DM
Spangfort
Michael D
MD
Blaser
Kurt
K
Akdis
Cezmi A
CA
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
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