The worldwide increase in the incidence of allergic diseases and the limited efficacy of current vaccines require the development of new efficient vaccination strategies. Based on PTD (protein transduction domain) technology, we have engineered MAT (modular antigen translocation) molecules, aimed to enhance antigen presentation through intracellular targeting of the MHC II presentation pathway. MAT vaccines consist of a cloning cassette, which fuses Tat (transactivator of transcription) peptide to a truncated Ii (invariant chain), which is able to target antigens to the nascent MHC II molecules in the trans-Golgi compartment. To test the efficacy of intracellular targeting, we engineered arrays of MAT-fusions and compared the effects of recombinant allergens, Tat-conjugated allergens and MAT-conjugated allergens for the ability to stimulate T-cell proliferation and cytokine production in human PBMC (peripheral blood mononuclear cell) cultures derived from allergic individuals, and to elicit protective immune responses in mice. MAT–vaccines induced a strong proliferation of PBMCs at a low concentration and induced a Th2/Treg (regulatory T-cell) cell shift in the cytokine profile, reflecting those reported in successfully desensitized allergic individuals. In allergic mouse models, we showed that MAT–vaccines are highly efficient in desensitizing mice and protect them from anaphylactic shock. The technology is applicable not only for the treatment of allergies, but also for the development of preventive vaccines in general.
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August 2007
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Conference Article|
July 20 2007
Targeting the MHC II presentation pathway in allergy vaccine development
C. Rhyner;
C. Rhyner
*Swiss Institute of Allergy and Asthma Research (SIAF), Obere Strasse 22, CH-7270 Davos, Switzerland
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T. Kündig;
T. Kündig
†University of Zürich, Clinic of Dermatology, Rämistrasse 100, CH-8091 Zürich, Switzerland
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C.A. Akdis;
C.A. Akdis
*Swiss Institute of Allergy and Asthma Research (SIAF), Obere Strasse 22, CH-7270 Davos, Switzerland
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R. Crameri
R. Crameri
1
*Swiss Institute of Allergy and Asthma Research (SIAF), Obere Strasse 22, CH-7270 Davos, Switzerland
1To whom correspondence should be addressed (email crameri@siaf.unizh.ch).
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Publisher: Portland Press Ltd
Received:
May 11 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (4): 833–834.
Article history
Received:
May 11 2007
Citation
C. Rhyner, T. Kündig, C.A. Akdis, R. Crameri; Targeting the MHC II presentation pathway in allergy vaccine development. Biochem Soc Trans 1 August 2007; 35 (4): 833–834. doi: https://doi.org/10.1042/BST0350833
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