Recombinant outer membrane vesicles coupled with cytokines act as high-performance adjuvants againstHelicobacter pyloriinfection in mice

Abstract The widespread prevalence of Helicobacter pylori ( H. pylori ) infection remains a great challenge to the human health. The existing vaccines are not ideal for preventing H. pylori infection; thus, exploring highly effective adjuvants may improve the immunoprotective efficacy of H. pylori vaccines. In a previous study, we found that outer membrane vesicles (OMVs), a type of nanoscale particle spontaneously produced by Gram-negative bacteria, could act as adjuvants to boost the immune response to vaccine antigens. In the present study, we explored the potential application of OMVs as delivery vectors for adjuvant development. We constructed recombinant OMVs containing cytokines interleukin 17A or interferon-γ and evaluated their function as adjuvants in combination with inactivated whole-cell vaccine (WCV) or UreB as vaccine antigens. Our results showed that recombinant OMVs as adjuvants could induce stronger humoral and mucosal immune responses in mice than wild-type H. pylori OMVs and the cholera toxin (CT) adjuvant. Additionally, the recombinant OMVs significantly promoted Th1/Th2/Th17-type immune responses. Furthermore, the recombinant OMV adjuvant induced more potent clearance of H. pylori than CT and wild-type OMVs. Our data suggest that the recombinant OMVs coupled with cytokines may become potent adjuvants for development of novel and effective vaccines against H. pylori infection. Importance Helicobacter pylori ( H. pylori ) is one of the important risk factors for gastric cancer, and its vaccine is crucial for its prevention and control. However, to date, no effective vaccine has been approved. Exploring novel and effective vaccine adjuvants may provide new perspectives and ideas for the development of H. pylori vaccines. Outer membrane vesicles (OMVs) deserve more attention as a novel form of vaccine and adjuvant. We have long focused on OMVs as vaccine adjuvants to enhance efficacy by delivering eukaryotic plasmid expressing immune promoting cytokines in wild-type OMVs. Our results are expected to provide a new adjuvant form for the development of H. pylori vaccine, and this adjuvant design strategy can also be used in the development of vaccines for other types of pathogens, including bacteria and even viruses.