Neutrophil Granule-Mimetic Emulsion Inducing Gastrointestinal Immunity against <i>Helicobacter pylori</i> via Subcutaneous Vaccination

<i>Helicobacter pylori</i> (<i>H. pylori</i>) infection is a leading cause of chronic gastritis, peptic ulcers, and gastric cancer. Although oral vaccines are promising for <i>H. pylori</i> 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 <i>H. pylori</i> 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 <i>H. pylori</i> 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 <i>H. pylori</i>.