IngentaConnect Targeting the MHC class II pathway of antigen presentation enhanc...

Authors: Martínez-Gómez, J. M.¹; Johansen, P.¹; Rose, H.²; Steiner, M.²; Senti, G.¹; Rhyner, C.³; Crameri, R.³; Kündig, T. M.¹

Source: Allergy, Volume 64, Number 1, January 2009 , pp. 172-178(7)

Publisher: Blackwell Publishing

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.

Keywords: allergy; immunotherapy; invariant chain; recombinant proteins; TAT protein

Document Type: Research article

DOI: 10.1111/j.1398-9995.2008.01812.x

Affiliations: 1: Unit for Experimental Immunotherapy, Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland 2: ImVisioN GmbH, Hannover, Germany 3: Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland

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Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapy