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 Fcγ1 and the major cat allergen Fel dl, as a proof of concept for a new approach to allergy immunotherapy. This Fcγ-Fel dl protein induced dose-dependent inhibition of Fel dl-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 Fcy-Fel dl protein also blocked in vivo reactivity in FceRIα transgenic mice passively sensitized with human IgE antibody to cat and in Balb/c mice actively sensitized against Fel dl. The Fcγ-Fel dl 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.