Allergenicity and immunogenicity of the major mugwort pollen allergen Art v 1 chemically modified by acetylation

• Published in: Clinical and experimental allergy 2009-03, Vol.39 (3), p.435-446
• Main Authors: Perovic, I., Milovanovic, M., Stanic, D., Burazer, L., Petrovic, D., Milcic-Matic, N., Gafvelin, G., Van Hage, M., Jankov, R., Velickovic, T. Cirkovic
• Format: Article
• Language: English
• Subjects: Acetylation; Adolescent; Adult; allergen-specific immunotherapy; Allergens - chemistry; Allergens - immunology; allergoid; Animals; Antibody Formation - immunology; Antigen-Antibody Reactions - immunology; Antigens, Plant; Art v 1; Basophil Degranulation Test; Basophils - immunology; Binding, Competitive - immunology; Biological and medical sciences; blocking antibodies; Cytokines - metabolism; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Hypersensitivity - immunology; Immunization; Immunoglobulin E - immunology; Immunoglobulin G - blood; Immunoglobulin G - immunology; Isoelectric Point; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Male; Middle Aged; Molecular Weight; mugwort pollen allergy; Plant Proteins - chemistry; Plant Proteins - immunology; Pollen - chemistry; Pollen - immunology; Rabbits; Young Adult
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2008.03158.x

Summary 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.