Abstract | BACKGROUND: Current s.c. allergen-specific immunotherapy (SIT) leads to amelioration of IgE-mediated allergy, but it requires numerous allergen injections over several years and is frequently associated with severe side-effects. The aim of this study was to test whether modified recombinant allergens can improve therapeutic efficacy in SIT while reducing allergic side-effects. METHODS: The major cat allergen Fel d 1 was fused to a TAT-derived protein translocation domain and to a truncated invariant chain for targeting the MHC class II pathway (MAT-Fel d 1). The immunogenicity was evaluated in mice, while potential safety issues were assessed by cellular antigen stimulation test (CAST) using basophils from cat-dander-allergic patients. RESULTS: MAT-Fel d 1 enhanced induction of Fel d 1-specific IgG2a antibody responses as well as the secretion of IFN-gamma and IL-2 from T cells. Subcutaneous allergen-specific immunotherapy of mice using the modified Fel d 1 provided stronger protection against anaphylaxis than SIT with unmodified Fel d 1, and MAT-Fel d 1 caused less degranulation of human basophils than native Fel d 1. CONCLUSION: MAT-Fel d 1 allergen enhanced protective antibody and Th1 responses in mice, while reducing human basophil degranulation. Immunotherapy using MAT-Fel d 1 allergen therefore has the potential to enhance SIT efficacy and safety, thus, shortening SIT. This should increase patient compliance and lower treatment costs.
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Authors | J M Martínez-Gómez, P Johansen, H Rose, M Steiner, G Senti, C Rhyner, R Crameri, T M Kündig |
Journal | Allergy
(Allergy)
Vol. 64
Issue 1
Pg. 172-8
(Jan 2009)
ISSN: 1398-9995 [Electronic] Denmark |
PMID | 19076537
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Allergens
- Glycoproteins
- Histocompatibility Antigens Class II
- Recombinant Proteins
- Fel d 1 protein, Felis domesticus
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Topics |
- Allergens
(therapeutic use)
- Animals
- Antibody Formation
(drug effects)
- Antigen Presentation
- Basophils
- Cats
- Cell Degranulation
(drug effects)
- Drug Delivery Systems
- Drug-Related Side Effects and Adverse Reactions
- Glycoproteins
(pharmacology, therapeutic use)
- Histocompatibility Antigens Class II
(metabolism)
- Humans
- Immunotherapy
(methods)
- Mice
- Recombinant Proteins
- Th1 Cells
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