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J Allergy Clin Immunol. 2017 Jun;139(6):1897-1905.e1. doi: 10.1016/j.jaci.2016.10.018. Epub 2016 Nov 19.

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

Author information

1
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
2
Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria.
3
Biomay AG, Vienna, Austria.
4
Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands; Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, The Netherlands.
5
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.

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.

OBJECTIVES:

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.

KEYWORDS:

Blocking antibodies; fish allergy; hypoallergenic parvalbumin mutant; specific immunotherapy

PMID:
27876628
PMCID:
PMC5438872
DOI:
10.1016/j.jaci.2016.10.018
[Indexed for MEDLINE]
Free PMC Article

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