Immunomodulation

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Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes

  1. Fariba Karamloo1,*,
  2. Peter Schmid-Grendelmeier1,2,
  3. Fatimah Kussebi1,
  4. Mübeccel Akdis1,
  5. Maria Salagianni3,
  6. Barbara R. von Beust2,
  7. Andrea Reimers4,
  8. Judith Zumkehr1,
  9. Lyudmilla Soldatova5,
  10. Zora Housley-Markovic5,
  11. Ulrich Müller4,
  12. Thomas Kündig2,
  13. David M. Kemeny3,
  14. Michael D. Spangfort7,
  15. Kurt Blaser1,
  16. Cezmi A. Akdis1

Article first published online: 4 OCT 2005

DOI: 10.1002/eji.200425522

Issue

European Journal of Immunology

European Journal of Immunology

Volume 35, Issue 11, pages 3268–3276, November 2005

Additional Information

How to Cite

Karamloo, F., Schmid-Grendelmeier, P., Kussebi, F., Akdis, M., Salagianni, M., von Beust, Barbara R., Reimers, A., Zumkehr, J., Soldatova, L., Housley-Markovic, Z., Müller, U., Kündig, T., Kemeny, David M., Spangfort, Michael D., Blaser, K. and Akdis, Cezmi A. (2005), Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes. Eur. J. Immunol., 35: 3268–3276. doi: 10.1002/eji.200425522

Author Information

  1. 1

    Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland

  2. 2

    Allergy Unit, Dept. of Dermatology, Zürich, Switzerland

  3. 3

    Department of Immunology, GKT School of Medicine, Rayne Institute, London, UK

  4. 4

    Medical Division, Hospital Berne-Ziegler, Bern, Switzerland

  5. 5

    Center for Drug Evaluation and Research, US Food and Drug Administration, Bethesda, USA

  6. 7

    ALK-Abello Inc., Hoersholm, Denmark

*Swiss Institute of Allergy and Asthma Research (SIAF), Obere Strasse 22, 7270 Davos, Switzerland, Fax: +41–81–410–08–40

Publication History

  1. Issue published online: 7 NOV 2005
  2. Article first published online: 4 OCT 2005
  3. Manuscript Accepted: 26 AUG 2005
  4. Manuscript Revised: 11 MAY 2005
  5. Manuscript Received: 3 AUG 2004

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Keywords:

  • Allergy;
  • T cells;
  • Antibodies;
  • Antigens/peptides/epitopes;
  • Vaccination

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 FcϵRI cross-linking in sensitized individuals.

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