title: Identification and characterization of major cat allergen Fel d 1 mimotopes on filamentous phage carriers.
abstract: Cat allergy is one of the most prevalent allergies worldwide and can lead to the development of rhinitis and asthma. Thus far, only allergen extracts from natural sources have been used for allergen-specific immunotherapy. However, extracts and whole allergens in immunotherapy present an anaphylaxis risk. Identification of allergen epitopes or mimotopes has an important role in development of safe and effective allergen-specific immunotherapy. Moreover, with a suitable immunogenic carrier, the absence of sufficient immune response elicited by short peptides could be surmounted. In this study, we identified five structural mimotopes of the major cat allergen Fel d 1 by immunoscreening with random peptide phage libraries. The mimotopes were computationally mapped to the allergen surface, and their IgE reactivity was confirmed using sera from cat-allergic patients. Importantly, the mimotopes showed no basophil activation of the corresponding cat-allergic patients, which makes them good candidates for the development of hypoallergenic vaccine. As bacteriophage particles are becoming increasingly recognized as immunogenic carriers, we constructed bacteriophage particles displaying multiple copies of each selected mimotope on major phage coat protein. These constructed phages elicited T cell-mediated immune response, which was predominated by the type 1 T cell response. Mimotopes alone contributed to the type 1 T cell response by promoting IL-2 production. Fel d 1 mimotopes, as well as their filamentous phage immunogenic carriers, represent promising candidates in the development of hypoallergenic vaccine against cat allergy.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Slovenia.
authors.forename: Jernej
authors.initials: J
authors.lastname: Luzar
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Slovenia.
authors.forename: Peter
authors.initials: P
authors.lastname: Molek
authors.affiliation: University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.
authors.forename: Mira
authors.initials: M
authors.lastname: Šilar
authors.affiliation: University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.
authors.forename: Peter
authors.initials: P
authors.lastname: Korošec
authors.affiliation: University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.
authors.forename: Mitja
authors.initials: M
authors.lastname: Košnik
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Slovenia.
authors.forename: Borut
authors.initials: B
authors.lastname: Štrukelj
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Slovenia. Electronic address: mojca.lunder@ffa.uni-lj.si.
authors.forename: Mojca
authors.initials: M
authors.lastname: Lunder
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D015549:Basophil Degranulation Test; D015153:Blotting, Western; D002415:Cats; D003888:Desensitization, Immunologic / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005822:Genetic Vectors; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000517:prevention & control*; D007118:Immunoassay; D017912:Inovirus; D018716:Molecular Mimicry; D019151:Peptide Library
chemical_list: D000485:Allergens; D000939:Epitopes; D006023:Glycoproteins; D019151:Peptide Library; C059296:Fel d 1 protein, Felis domesticus
keywords: Cat allergy; Fel d 1; Filamentous phage carrier; Mimotopes