Residual Allergenic Risk of Digested Egg Ovotransferrin Revealed by Integrated <i>In Vitro</i> and <i>In Vivo</i> Models

Ovotransferrin (OVT), a nutritionally valuable egg-white protein, also acts as a notable food allergen. This study systematically evaluated the residual allergenic risk of OVT after simulated gastrointestinal digestion by integrating <i>in vitro</i> and <i>in vivo</i> models. Although gastrointestinal digestion markedly degraded OVT, a residual intact protein persisted. The digestion products exhibited reduced IgE-binding and degranulation-inducing activities but showed enhanced intestinal epithelial transport and dendritic cell uptake. Consistent with these findings, BALB/c mice sensitized with the OVT final digestion products (DPs) displayed attenuated allergic symptoms and Th2-skewed immune responses compared with those of the mice sensitized with OVT, yet retained mild allergenic reactivity. These findings demonstrate that gastrointestinal digestion cannot completely eliminate the allergenic potential of OVT, underscoring a residual risk that should be carefully considered in the safety evaluation and formulation of infant nutritional proteins.