title: Blocking antibodies induced by immunization with a hypoallergenic parvalbumin mutant reduce allergic symptoms in a mouse model of fish allergy.
abstract: BACKGROUND
  Fish is a frequent elicitor of severe IgE-mediated allergic reactions. Beside avoidance, there is currently no allergen-specific therapy available. Hypoallergenic variants of the major fish allergen, parvalbumin, for specific immunotherapy based on mutation of the 2 calcium-binding sites have been developed.
  
  
  OBJECTIVE
  This study sought to establish a mouse model of fish allergy resembling human disease and to investigate whether mouse and rabbit IgG antibodies induced by immunization with a hypoallergenic mutant of the major carp allergen protect against allergic symptoms in sensitized mice.
  
  
  METHODS
  C3H/HeJ mice were sensitized with recombinant wildtype Cyp c 1 or carp extract by intragastric gavage. Antibody, cellular immune responses, and epitope specificity in sensitized mice were investigated by ELISA, rat basophil leukemia assay, T-cell proliferation experiments using recombinant wildtype Cyp c 1, and overlapping peptides spanning the Cyp c 1 sequence. Anti-hypoallergenic Cyp c 1 mutant mouse and rabbit sera were tested for their ability to inhibit IgE recognition of Cyp c 1, Cyp c 1-specific basophil degranulation, and Cyp c 1-induced allergic symptoms in the mouse model.
  
  
  RESULTS
  A mouse model of fish allergy mimicking human disease regarding IgE epitope recognition and symptoms as close as possible was established. Administration of antisera generated in mice and rabbits by immunization with a hypoallergenic Cyp c 1 mutant inhibited IgE binding to Cyp c 1, Cyp c 1-induced basophil degranulation, and allergic symptoms caused by allergen challenge in sensitized mice.
  
  
  CONCLUSIONS
  Antibodies induced by immunization with a hypoallergenic Cyp c 1 mutant protect against allergic reactions in a murine model of fish 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: Raphaela
authors.initials: R
authors.lastname: Freidl
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: Antonia
authors.initials: A
authors.lastname: Gstoettner
authors.affiliation: Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Baranyi
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: Ines
authors.initials: I
authors.lastname: Swoboda
authors.affiliation: Biomay AG, Vienna, Austria.
authors.forename: Frank
authors.initials: F
authors.lastname: Stolz
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: Margarete
authors.initials: M
authors.lastname: Focke-Tejkl
authors.affiliation: Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wekerle
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands; Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: van Ree
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: Rudolf
authors.initials: R
authors.lastname: Valenta
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. Electronic address: birgit.linhart@meduniwien.ac.at.
authors.forename: Birgit
authors.initials: B
authors.lastname: Linhart
mesh_terms: D000485:Allergens / Q000235:genetics / Q000276:immunology*; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology*; D001491:Basophils / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000276:immunology*; D002347:Carps / Q000276:immunology; D015550:Cell Degranulation; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D005260:Female; D029941:Fish Proteins / Q000235:genetics / Q000276:immunology*; D005512:Food Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008809:Mice, Inbred C3H; D009154:Mutation; D010320:Parvalbumins / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D051381:Rats
chemical_list: D000485:Allergens; D019138:Antibodies, Blocking; D002135:Calcium-Binding Proteins; C454159:Cyp c 1.01 protein, carp; D029941:Fish Proteins; D007106:Immune Sera; D007074:Immunoglobulin G; D010320:Parvalbumins; D007073:Immunoglobulin E
keywords: Blocking antibodies; fish allergy; hypoallergenic parvalbumin mutant; specific immunotherapy