Potent IgE-Mediated Allergenic Reduction in Human Serum by Casein-Polyphenol Conjugates Makes Personalized Oral Immunotherapy Credible.

This study describes a potent hypoallergenic casein-polyphenol formula based on preclinical assays of serum samples from patients allergic to cow's milk proteins. Despite some variability among patients, results showed a significant IgE-binding reduction. This proof of concept indicates the reliability of altering the native structure and potential epitopes of allergens by natural polyphenols, consistent with previous studies monitoring amide bonding by vibrational spectroscopy. Structural predictions, binding pocket scouting, and molecular docking were used to explore the nature of the binding between polyphenols and casein isoforms. In silico modeling identified the interaction of polyphenol-protein hybrids with IgE-binding epitopes in α-S1, α-S2, and β-caseins, albeit only one in κ-casein, which provides a molecular basis for the clinically observed hypoallergenicity. Overall, preclinical analysis holds promise for oral immunotherapy to end food sensitivity and reduce the risk of life-threatening anaphylaxis. Parallel bioassays, however, with β-lactoglobulin, another cow's milk allergen, afforded promising results.