BACKGROUND: Previously, the protective farm effect was imitated using the whey protein beta-lactoglobulin (BLG) that is spiked with iron-flavonoid complexes. Here, we formulated for clinical translation a lozenge as food for special medical purposes (FSMP) using catechin-iron complexes as ligands for BLG. The lozenge was tested in vitro and in a therapeutical BALB/c mice model. METHODS: Binding of iron-catechin into BLG was confirmed by spectroscopy and docking calculations. Serum IgE binding of children allergic or tolerating milk was assessed to loaded (holo-) versus empty (apo-) BLG and for human mast cell degranulation. BLG and Bet v 1 double-sensitized mice were orally treated with the holoBLG or placebo lozenge, and immunologically analysed after systemic allergen challenge. Human PBMCs of pollen allergic subjects were flow cytometrically assessed after stimulation with apoBLG or holoBLG using catechin-iron complexes as ligands. RESULTS: One major IgE and T cell epitope were masked by catechin-iron complexes, which impaired IgE binding of milk-allergic children and degranulation of mast cells. In mice, only supplementation with the holoBLG lozenge reduced clinical reactivity to BLG and Bet v 1, promoted Tregs, and suppressed antigen presentation. In allergic subjects, stimulation of PBMCs with holoBLG led to a significant increase of intracellular iron in circulating CD14+ cells with significantly lower expression of HLADR and CD86 compared to their stimulation with apoBLG. CONCLUSION: The FSMP lozenge targeted antigen presenting cells and dampened immune activation in human immune cells and allergic mice in an antigen-non-specific manner, thereby conferring immune resilience against allergic symptoms.

Allergy Therapeutics Worthing UK

Bencard Allergie GmbH Munich Germany

Biomedical International R D GmbH Vienna Austria

Biotechnology Department ETSIAAB Center for Plant Biotechnology and Genomics CBGP Technical University of Madrid Madrid Spain

Childrens Hospital Bambino Gesù Rome Italy

Comparative Medicine The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna Medical University Vienna and University of Vienna Vienna Austria

Department of Cell Biology and Genetics Faculty of Science Palacky University Olomouc Czech Republic

Division of Pharmacology Faculty of Science Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands

Institute of Pathophysiology and Allergy Research Center of Pathophysiology Infectiology and Immunology Medical University of Vienna Vienna Austria

Laboratory Medicine and Immunology Department Faculty of Medicine Menoufia University Shibin El Kom Egypt

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Nutritional Provision of Iron Complexes by the Major Allergen Alt a 1 to Human Immune Cells Decreases Its Presentation

Pre-asthma: a useful concept for prevention and disease-modification? A EUFOREA paper. Part 1-allergic asthma

Binding to Iron Quercetin Complexes Increases the Antioxidant Capacity of the Major Birch Pollen Allergen Bet v 1 and Reduces Its Allergenicity