Allergenicity and immunogenicity of the major mugwort pollen allergen Art v 1 chemically modified by acetylation |
| |
Authors: | I. Perovic M. Milovanovic D. Stanic L. Burazer D. Petrovic N. Milcic-Matic G. Gafvelin M. van Hage R. Jankov T. Cirkovic Velickovic |
| |
Affiliation: | Faculty of Chemistry, Department of Biochemistry, University of Belgrade, Belgrade,;Department of Pulmology, Allergy and Clinical Immunology, Zvezdara University Hospital, Belgrade,;Department of Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Belgrade,;Department of Allergy, Institute of Immunology and Virology 'Torlak', Belgrade,;Department of Dermatology, School of Veterinary Medicine, Belgrade, Serbia and;Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden |
| |
Abstract: | Background Treating allergies with modified allergens is an approach to make the treatment safer and more efficient. Art v 1 is the most prominent allergen of mugwort pollen and a significant cause of hayfever around Europe. The aim of this study was to reduce the allergenicity of Art v 1 by acetylation, and to investigate the capacity of the modified protein to generate blocking antibodies. Methods The reduction of allergenicity of Art v 1 following acetylation was monitored by immunoblot, ELISA inhibition using a pool of sera from mugwort pollen allergic patients, basophil activation assay and by skin prick testing of mugwort-allergic patients. Rabbits were immunized against Art v 1 and acetylated Art v 1 (acArt v 1) and the rabbit antisera were tested for their capacity to block human IgE binding in ELISA. Human T cell proliferation against Art v 1 and acArt v 1 was examined in peripheral blood mononuclear cells (PBMCs) of mugwort pollen allergic patients and cytokine release in PBMC cultures was monitored. Results Acetylation of Art v 1 gave a derivative of reduced allergenicity in the in vitro and ex vivo tests applied. The skin test reactivity to acArt v 1 was significantly reduced in 19 patients when compared with the reactivity to Art v 1. Rabbit antibodies to acArt v 1 and Art v 1 showed similar capacity to block human IgE binding to Art v 1 in inhibition ELISA. Both proteins were able to induce proliferation of PBMCs and CD3/CD4+ cells of mugwort-allergic patients. Release of IL-5 was significantly reduced in cultures stimulated with acArt v 1. Conclusions Art v 1 modified by acetylation had a significantly reduced allergenicity in vitro and in vivo , while its immunogenicity was retained. Modification of allergens by acetylation could be a new strategy for allergen-specific immunotherapy. |
| |
Keywords: | acetylation allergen-specific immunotherapy allergoid Art v 1 blocking antibodies mugwort pollen allergy |
|
|