Bridging Systemic Immunity with Gastrointestinal Immune Responses via Oil‐in‐Polymer Capsules

As peripheral lymphocytes are typically excluded from the gastrointestinal lymph tissues, current parenteral vaccinations fail to simultaneously induce systemic and mucosal responses. To break the natural barrier, “immunoticket” capsules are developed and heralded, which are designed with positive charged shells and oily core to spatiotemporally deliver antigens and all‐trans retinoic acid (RA). After intramuscular vaccinations, these capsules function as an immunoticket to cultivate peripheral dendritic cells (DCs) with gut‐homing receptors (CCR9). By hitchhiking on the concentration gradient of the CC‐motif chemokine ligand 25 (CCL25), the primed DCs would home to the gut associated lymphoid tissues (GALTs) and induce antigen‐specific IgA secretion and T cell engagements. Compared with the currently employed RA‐involving formulations, the immunoticket capsules stimulate enhanced RA‐mediated gut‐tropism by mounting the inflammatory innate immunity. Through controlling the RA payload, the potential regulatory T cell engagement is circumvented. In ovalbumin (OVA) and EV71 vaccinations, the immunoticket capsules induce potent serum IgG titer and antigen‐specific cytotoxic T cells in the peripheral lymph tissues, as well as robust IgA secretion and T cell engagements on gastrointestinal sites. The data suggest the potential of the immunotickets to serve as a facile, effective, and safe strategy to provide comprehensive immune responses against gastrointestinal infections and diseases Parenteral vaccinations are typically incompetent in inducing mucosal immune responses. Oil‐in‐polymer capsules are developed to co‐deliver antigens and retinoic acid. These capsules function as an “immunoticket” to cultivate peripheral lymphocytes hitchhiking on the “express train” of the chemokine (C‐C motif) ligand (CCL25) concentration gradient to the gastrointestinal tissues, and thus simultaneously provoke the gastrointestinal and systemic immune activations.