Epitopes described in "A hypoallergenic cat vaccine based on Fel d 1-derived peptides fused to hepatitis B PreS."

Article Authors:Katarzyna Niespodziana; Margarete Focke-Tejkl; Birgit Linhart; Vera Civaj; Katharina Blatt; Peter Valent; Marianne van Hage; Hans Grönlund; Rudolf Valenta
Article Title:A hypoallergenic cat vaccine based on Fel d 1-derived peptides fused to hepatitis B PreS.
Reference Detail
Reference ID:1021971
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.
Affiliations:Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Reference Type:Literature
PubMed ID:21411130
Journal:J Allergy Clin Immunol
Journal Volume:127
Article Pages:1562-70.e6
Journal ISSN:0091-6749
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
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)
Curation Last Updated:2015-08-05 20:01:30