Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapy |
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Authors: | J M Martínez-Gómez P Johansen H Rose M Steiner G Senti C Rhyner R Crameri T M Kündig |
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Institution: | Unit for Experimental Immunotherapy, Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland;;ImVisioN GmbH, Hannover, Germany;;Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland |
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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-γ 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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Keywords: | allergy immunotherapy invariant chain recombinant proteins TAT protein |
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