Orally-administered outer-membrane vesicles from Helicobacter pylori reduce H. pylori infection via Th2-biased immune responses in mice

Abstract

ABSTRACT As the trend of antibiotic resistance has increased, prevention and treatment of Helicobacter pylori infection have been challenged by the fact that no vaccines preventing H. pylori infection are available. Scientists continue to make sustained efforts to find better vaccine formulations and adjuvants to eradicate this chronic infection. In this study, we systemically analyzed the protein composition and potential vaccine function of outer-membrane vesicles (OMVs) derived from gerbil-adapted H. pylori strain 7.13. In total, we identified 169 proteins in H. pylori OMVs and found that outer-membrane, periplasmic and extracellular proteins (48.9% of the total proteins) were enriched. Furthermore, we evaluated the immune protective response of H. pylori OMVs in a C57BL/6 mouse model, and mice were orally immunized with OMVs or the H. pylori whole cell vaccine (WCV) alone, with or without cholera toxin (CT) as an adjuvant. The data demonstrated that oral immunization with OMVs can elicit a strong humoral and significantly higher mucosal immune response than the group immunized with the WCV plus the CT adjuvant. Moreover, our results also confirmed that OMVs predominantly induced T helper 2 (Th2)-biased immune responses that can significantly reduce bacterial loads after challenging with the H. pylori Sydney Strain 1 (SS1). In summary, OMVs as new antigen candidates in vaccine design would be of great value in controlling H. pylori infection.