Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes
✍ Scribed by Fariba Karamloo; Peter Schmid-Grendelmeier; Fatimah Kussebi; Mübeccel Akdis; Maria Salagianni; Barbara R. von Beust; Andrea Reimers; Judith Zumkehr; Lyudmilla Soldatova; Zora Housley-Markovic; Ulrich Müller; Thomas Kündig; David M. Kemeny; Michael D. Spangfort; Kurt Blaser; Cezmi A. Akdis
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 307 KB
- Volume
- 35
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
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 A 2 (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 FceRI cross-linking in sensitized individuals.