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| Article Authors: | Katarzyna Niespodziana; Margarete Focke-Tejkl; Birgit Linhart; Vera Civaj; Katharina Blatt; Peter Valent; Marianne van Hage; Hans Grönlund; Rudolf Valenta |
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| Article Title: | A hypoallergenic cat vaccine based on Fel d 1-derived peptides fused to hepatitis B PreS. |
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| Reference ID: | 1021971 |
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| Abstract: | BACKGROUND: Allergen-specific immunotherapy is clinically effective for the treatment of cat allergy but shows a high rate of side effects. OBJECTIVE: We sought to engineer recombinant fusion proteins for cat immunotherapy that allow reducing both IgE-mediated and T cell-mediated side effects. METHODS: Fusion proteins consisting of the hepatitis B virus-derived PreS domain and 2 nonallergenic Fel d 1-derived peptides were expressed in Escherichia coli and purified. IgE reactivity and allergenic activity of Fel d 1 and the fusion proteins were compared by using IgE-binding assays and basophil activation tests in patients with cat allergy. Mice and rabbits were immunized subcutaneously with Fel d 1 and the fusion proteins to investigate the allergenicity of the vaccines and the development of Fel d 1-specific IgG antibodies. RESULTS: The recombinant fusion proteins showed no relevant IgE reactivity and exhibited more than 1000-fold reduced allergenic activity in basophil activation tests. On immunization of mice and rabbits, the fusion proteins induced Fel d 1-specific IgG antibodies that inhibited the binding of allergic patients' IgE to the allergen without allergic sensitization to Fel d 1. CONCLUSION: The described recombinant fusion proteins exhibit strongly reduced IgE-mediated allergenic activity, contain less than 40% of the Fel d 1 sequence, and thus lack many of the specific T-cell epitopes. Therefore they should represent safe vaccines for the treatment of cat allergy. |
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| Affiliations: | Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. |
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| Date: | 2011 |
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| Reference Type: | Literature |
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| PubMed ID: | 21411130 |
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| Journal: | J Allergy Clin Immunol |
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| Journal Volume: | 127 |
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| Article Pages: | 1562-70.e6 |
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| Journal ISSN: | 0091-6749 |
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| Article Chemical List: | Allergens;ENPP3 protein, human;Fel d 1 protein, Felis domesticus;Glycoproteins;Hepatitis B Surface Antigens;Immunoglobulin G;Recombinant Fusion Proteins;Vaccines, Synthetic;Immunoglobulin E;Phosphoric Diester Hydrolases;Pyrophosphatases |
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| Article MeSH List: | Allergens(chemistry; genetics; immunology); Amino Acid Sequence; Animals; Basophils(immunology); Case-Control Studies; Cats; Desensitization, Immunologic(methods); Glycoproteins(chemistry; genetics; immunology); Hepatitis B Surface Antigens(chemistry; genetics; immunology); Humans; Hypersensitivity(immunology; therapy); Immunoglobulin E(metabolism); Immunoglobulin G(biosynthesis); Mice; Molecular Sequence Data; Pets(immunology); Phosphoric Diester Hydrolases(metabolism); Protein Conformation; Protein Engineering; Pyrophosphatases(metabolism); Rabbits; Rats; Recombinant Fusion Proteins(chemistry; genetics; immunology); T-Lymphocytes(immunology); Vaccines, Synthetic(chemistry; genetics; immunology) |
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| Curation Last Updated: | 2012-05-31 20:50:06 |
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