Liposomal hydrogel-based oral vaccine delivery for targeted induction of intestinal mucosal immunity

Oral vaccines have attracted considerable attention due to their advantages of convenient administration and ability to induce mucosal immunity. However, unfavorable conditions such as the gastrointestinal barrier and acidic environment constrain their immunogenic efficacy. To address these issues, a novel oral vaccine delivery platform has been developed, in which mannose-decorated liposomes are complexed with antigen and retinoic acid, then enveloped by a thiolated alginate gel microsphere (MLip@Gel). Mannose-modified liposomes adsorb porcine epidemic diarrhea virus (PEDV) through electrostatic interactions, targeting intestinal macrophages and enhancing uptake. Thiol-modified sodium alginate is used as a gel shell, preventing PEDV from being destroyed in the stomach and promoting retention in the intestines. Retinoic acid (RA) facilitates the differentiation of cells that promote secretory IgA production. The delivery system maintain stability under acidic conditions, while decomposing at pH ≥ 6.8 to release the antigen. Experiments on mice demonstrate that PR-MLip@Gel can induce a high level of α4β7⁺CCR9⁺ cell activation and IgA level, compared to PEDV(IM) group. Systemic responses, such as IgG and CD4⁺/CD8⁺ T, B cells, are also significantly increased. The challenge experiments demonstrate that piglets immunized with PR-MLip@Gel exhibit better protection against PEDV infection, as PR-MLip@Gel can simultaneously induce robust mucosal immunity and humoral immunity. These findings suggest that the oral vaccine effectively induces strong mucosal and systemic immune responses, offering a promising strategy for developing oral vaccines against intestinal infectious diseases.