A chimeric human-cat fusion protein blocks cat-induced allergy.
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 Fcgamma1 and the major cat allergen Fel d1, as a proof of concept for a new approach to allergy immunotherapy. This Fcgamma-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 Fcgamma-Fel d1 protein also blocked in vivo reactivity in FcepsilonRIalpha transgenic mice passively sensitized with human IgE antibody to cat and in Balb/c mice actively sensitized against Fel d1. The Fcgamma-Fel d1 protein alone did not induce mediator release. Chimeric human Fcgamma-allergen fusion proteins may provide a new therapeutic platform for the immune-based therapy of allergic disease.
Zhu
Daocheng
D
The Hart and Louise Lyon Laboratory, Division of Clinical Immunology/Allergy, Department of Medicine, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, California 90095-1680, USA. dczhu@ucla.edu
Kepley
Christopher L
CL
Zhang
Ke
K
Terada
Tetsuya
T
Yamada
Takechiyo
T
Saxon
Andrew
A
D000818:Animals; D002415:Cats; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014612:Vaccines / Q000276:immunology* / Q000627:therapeutic use
D006023:Glycoproteins; D011993:Recombinant Fusion Proteins; D014612:Vaccines; C059296:Fel d 1 protein, Felis domesticus