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A chimeric human-cat fusion protein blocks cat-induced allergy

Nature Medicine volume 11, pages 446–449 (2005)Cite this article

Abstract

Animal allergens are an important cause of asthma and allergic rhinitis. We designed and tested a chimeric human-cat fusion protein composed of a truncated human IgG Fcγ1 and the major cat allergen Fel d1, as a proof of concept for a new approach to allergy immunotherapy. This Fcγ-Fel d1 protein induced dose-dependent inhibition of Fel d1-driven IgE-mediated histamine release from cat-allergic donors' basophils and sensitized human cord blood-derived mast cells. Such inhibition was associated with altered Syk and ERK signaling. The Fcγ-Fel d1 protein also blocked in vivo reactivity in FcεRIα transgenic mice passively sensitized with human IgE antibody to cat and in Balb/c mice actively sensitized against Fel d1. The Fcγ-Fel d1 protein alone did not induce mediator release. Chimeric human Fcγ-allergen fusion proteins may provide a new therapeutic platform for the immune-based therapy of allergic disease.

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Figure 1: GFD inhibits human basophil and mast cell degranulation.
Figure 2: GFD inhibits FcεRI-mediated Syk and ERK phosphorylation.
Figure 3: GFD inhibits IgE-mediated degranulation in FcεRIα transgenic mice.
Figure 4: GFD blocks Fel d1-induced allergic response in mice.

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Acknowledgements

Supported by an USPHS-NIH grant, AI-15251 to A.S. We thank S.L. Morrison, R. Trinh and L. A. Chan for technical advice and for providing some experimental materials. C.L.K. was supported by a grant from the American Lung Association and the AD Williams Foundation at VCU, and the Food Allergy and Anaphylaxis Network. We also thank J.P. Kinet for providing the human FcεRIα transgenic mice. We are grateful to T.H. Sulahian and P.M. Guyre for the Fel d1 cDNA construct. We thank M. Jyrala, L. Zhang, and M. Rainof for technical assistance.

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  1. Daocheng Zhu, Christopher L Kepley, Ke Zhang and Tetsuya Terada: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Clinical Immunology/Allergy, Department of Medicine, The Hart and Louise Lyon Laboratory, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, 90095-1680, California, USA

    Daocheng Zhu, Ke Zhang, Tetsuya Terada, Takechiyo Yamada & Andrew Saxon

  2. Division of Rheumatology, Department of Internal Medicine, Allergy and Immunology, Room 4-115B, McGuire Hall, 1112 East Clay Street, Virginia Commonwealth University, Richmond, 23298-0263, Virginia, USA

    Christopher L Kepley

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Correspondence to Daocheng Zhu or Andrew Saxon.

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Competing interests

Daocheng Zhu, Zhang Ke and Andrew Saxon are coinventors on the patent held by the University of California for gamma-allergen proteins.

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Zhu, D., Kepley, C., Zhang, K. et al. A chimeric human-cat fusion protein blocks cat-induced allergy. Nat Med 11, 446–449 (2005). https://doi.org/10.1038/nm1219

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