Prolonged antigen-exposure with carbohydrate particle based vaccination prevents allergic immune responses in sensitized mice |
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Authors: | S Thunberg T Neimert-Andersson Q Cheng F Wermeling U Bergström L Swedin S-E Dahlén E Arnér A Scheynius M C I Karlsson G Gafvelin M van Hage H Grönlund |
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Institution: | Clinical Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden;;Clinical Allergy Research Unit, Department of Medicine, Karolinska Institutet Solna, Stockholm, Sweden;;MBB, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden;;Department of Environmental Toxicology, Uppsala University, Uppsala, Sweden;;The National Institute of Environmental Medicine and the Centre for Allergy Research, Karolinska Institute, Stockholm, Sweden |
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Abstract: | Background: Defined particles carrying tightly bound allergens at high density have been suggested as alternatives in allergy vaccination. Carbohydrate based particles (CBP), sized 2 μm, provide a platform for covalent coupling of allergens. Objective: To investigate the mechanisms of antigen presentation by CBP, as well as cellular and humoral responses after vaccination with the major cat allergen Fel d 1, covalently coupled to CBP. Methods: Mice ( n = 10/group) were subcutaneously vaccinated with CBP-rFel d 1, CBP or phosphate buffer saline (PBS) before sensitization with rFel d 1 and challenged with cat dander extract. Fluorescent and 75Se-radiolabeled tracking of allergens and particles were performed with flow cytometry and whole-body autoradiography. Humoral, cellular and regulatory immune responses were analyzed by ELISA and flow cytometry. Cytokines were measured in bronchoalveolar lavage fluid and splenocyte cultures. Results: CBP-rFel d 1 prevented induction of airway inflammation and induced allergen-specific T-cell anergy. CBP-rFel d 1 also induced rapid IgM and IgG1-responses compared with soluble rFel d 1. Particles were phagocytosed by antigen-presenting cells and transported to draining lymph nodes and spleen. Moreover, antigen coupled to CBP remained longer at the injection site compared with alum. Conclusions: Covalent coupling of rFel d 1 to CBP induces rapid antibody production, prevents induction of allergic immune responses and systemic allergen spreading. Thus, CBP comprise several attractive adjuvant features for use in allergy vaccination. Clinical Implications: Prolonged allergen exposure through covalent coupling to particles suitable for phagocytosis, provides an adjuvant for safer and efficient allergy vaccination. |
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Keywords: | adjuvant allergy particles rFel d 1 vaccination |
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