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Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapy
Author(s) -
MartínezGómez J. M.,
Johansen P.,
Rose H.,
Steiner M.,
Senti G.,
Rhyner C.,
Crameri R.,
Kündig T. M.
Publication year - 2009
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2008.01812.x
Subject(s) - immunogenicity , immunology , medicine , allergen , basophil activation , allergen immunotherapy , immunotherapy , allergy , immunoglobulin e , antigen , degranulation , antibody , basophil , immune system , receptor
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.