Blocking antibodies induced by immunization with a hypoallergenic parvalbumin mutant reduce allergic symptoms in a mouse model of fish allergy

Publication date: Available online 19 November 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Raphaela Freidl, Antonia Gstoettner, Ulrike Baranyi, Ines Swoboda, Frank Stolz, Margarete Focke-Tejkl, Thomas Wekerle, Ronald van Ree, Rudolf Valenta, Birgit Linhart
BackgroundFish 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 two calcium-binding sites have been developed.ObjectiveTo 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, mCyp c 1, protect against allergic symptoms in sensitized mice.MethodsC3H/HeJ mice were sensitized with rCyp c 1 or carp extract by intragastric gavage. Antibody, cellular immune responses and epitope specificity in sensitized mice were investigated by ELISA, RBL assay, T cell proliferation experiments using rCyp c 1 and overlapping peptides spanning the Cyp c 1 sequence. Anti-mCyp c 1 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.ResultsA 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.ConclusionAntibodies induced by immunization with a hypoallergenic Cyp c 1 mutant protect against allergic reactions in a murine model of fish allergy.Clinical implicationsIgG antibodies induced by vaccination with a hypoallergenic Cyp c 1 mutant may protect against fish allergy.

Teaser

Vaccination with a recombinant hypoallergenic Cyp c 1 mutant induces Cyp c 1-specific IgG antibodies which block IgE binding to Cyp c 1 and protected against symptoms of fish allergy in a mouse model.


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