Neutrophil Granule-Mimetic Emulsion Inducing Gastrointestinal Immunity against Helicobacter pylori via Subcutaneous Vaccination.

Helicobacter pylori (H. pylori) infection is a leading cause of chronic gastritis, peptic ulcers, and gastric cancer. Although oral vaccines are promising for H. pylori prevention, their effectiveness is greatly limited by gastrointestinal barriers and easily induced immune tolerance. In this study, we developed a neutrophil granule-mimetic emulsion to induce gastrointestinal immunity via subcutaneous vaccination. This emulsion, solely stabilized by lactoferrin─a key component of neutrophil granules─functioned as a neutrophil sensitizer, recruiting neutrophils and antigen-presenting cells and amplifying their interactions to initiate innate and adaptive immune responses. By incorporating retinoic acid and CpG, this emulsion enhanced the expression of the gut-homing receptor CCR9 in immune cells, enabling their migration to the gut, thereby promoting germinal center formation, and establishing tissue-resident memory T cells in the mesenteric lymph nodes. This ultimately elevated robust mucosal and systemic immune responses. By loading bivalent H. pylori antigens, this emulsion elicited robust systemic and mucosal antibody responses, accompanied by mixed Th1 and Th17 cellular responses, achieving up to 91.3% protection against H. pylori infection. Our work underscored the potential of the neutrophil granule-mimicking strategy for bridging innate and adaptive immunity and demonstrated a subcutaneously administered platform for developing mucosal vaccines against H. pylori.