title: A hypoallergenic cat vaccine based on Fel d 1-derived peptides fused to hepatitis B PreS.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Niespodziana
authors.forename: Margarete
authors.initials: M
authors.lastname: Focke-Tejkl
authors.forename: Birgit
authors.initials: B
authors.lastname: Linhart
authors.forename: Vera
authors.initials: V
authors.lastname: Civaj
authors.forename: Katharina
authors.initials: K
authors.lastname: Blatt
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Marianne
authors.initials: M
authors.lastname: van Hage
authors.forename: Hans
authors.initials: H
authors.lastname: Grönlund
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D001491:Basophils / Q000276:immunology; D016022:Case-Control Studies; D002415:Cats; D003888:Desensitization, Immunologic / Q000379:methods*; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D057805:Pets / Q000276:immunology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011487:Protein Conformation; D015202:Protein Engineering; D011755:Pyrophosphatases / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D000485:Allergens; C427944:ENPP3 protein, human; D006023:Glycoproteins; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; C059296:Fel d 1 protein, Felis domesticus