An Engineered Nano-Vesicle Adjuvant Platform (ENAP) for Cytokine Delivery Enables a Novel Antigen-Coordinated Vaccine Against Helicobacter pylori.

Despite the considerable potential of Helicobacter pylori (H. pylori) vaccines, their clinical efficacy has been hampered by inadequate mucosal immunity and suboptimal Th1/Th17 polarization. To address this, we engineered a novel nano-adjuvant system using LPS-modified recombinant outer membrane vesicles (rOMVs) derived from H. pylori to function as a programmable cytokine presentation platform. This engineered nano-vesicle adjuvant platform (ENAP) confers unique synergistic advantages, including efficient delivery of key immunomodulatory cytokines such as IL-17A and IFN-γ, and potent activation of antigen-specific T-cell immunity. Following immunization, the platform significantly enhanced antigen-specific mucosal IgA and systemic IgG2c/IgG1 antibody responses. It further induced a pronounced Th1/Th17-skewed cellular immune response, resulting in a substantial reduction in bacterial colonization in a protective challenge model. Collectively, our study proposes a versatile and customizable nanotechnology strategy for reprogramming local and systemic immunity through targeted cytokine delivery, offering a promising avenue for the development of next-generation mucosal vaccine adjuvants against H. pylori and other pathogens.