A major allergen gene-fusion protein for potential usage in allergen-specific immunotherapy

Kussebi, F. and Karamloo, F. and Rhyner, C. and Schmid-Grendelmeier, P. and Salagianni, M. and Mannhart, C. and Akdis, M. and Soldatova, L. and Markovic-Housley, Z. and von Beust, B. R. and Kundig, T. and Kemeny, D. M. and Blaser, K. and Crameri, R. and Akdis, C. A.. (2005) A major allergen gene-fusion protein for potential usage in allergen-specific immunotherapy. The journal of allergy and clinical immunology, Vol. 115, H. 2. pp. 323-329.

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Official URL: http://edoc.unibas.ch/dok/A5258244

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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. CONCLUSION: The novel fusion protein of 2 major allergens bypasses IgE binding and mast cell/basophil IgE FcepsilonRI crosslinking and protects from IgE development.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Schirmer)
UniBasel Contributors:Schirmer, Tilman and Housley-Markovic, Zora
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:14 Sep 2012 06:50
Deposited On:22 Mar 2012 13:29

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