Combined IgE neutralization and Bifidobacterium longum supplementation reduces the allergic response in models of food allergy

IgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgE TRAP, to reduce the risk of IgG1 Fc-mediated side effects. IgE TRAP shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgE TRAP in food allergy models when combined with Bifidobacterium longum , which results in mast cell number and free IgE levels. The combination of IgE TRAP and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.