Abstract
Helicobacter pylori(H. pylori), a gram-negative bacterium in the human stomach with global prevalence, is relevant to chronic gastrointestinal diseases. Due to its increasing drug resistance and the low protective efficacy of some anti-H. pylori vaccines, it is necessary to find a suitable adjuvant to improve antigen efficiency. In our previous study, we determined that outer membrane vesicles (OMVs), a multicomponent secretion generated by gram-negative bacteria, of H. pylori were safe and could induce long-term and robust immune responses against H. pylori in mice. In this study, we employed two common vaccines, outer membrane proteins (OMPs) and whole cell vaccine (WCV) to assess the adjuvanticity of OMVs in mice. A standard adjuvant, cholera toxin (CT), was used as a control. Purified H. pylori OMVs used as adjuvants generated lasting anti-H. pylori resistance for 12 weeks. Additionally, both systematic and gastric mucosal immunity, as well as humoral immunity, of mice immunized with vaccine and OMVs combinations were significantly enhanced. Moreover, OMVs efficiently promoted Th1 immune response, but the response was skewed toward Th2 and Th17 immunity when compared with that induced by the CT adjuvant. Most importantly, OMVs as adjuvants enhanced the eradication of H. pylori. Thus, OMVs have potential applications as adjuvants in the development of a new generation of vaccines to treat H. pylori infection.
Highlights
Helicobacter pylori (H. pylori), a gram-negative bacterium colonizing the mucus layer over the gastric epithelium, has been implicated in the pathogenesis of chronic gastritis and peptic ulcer (Marshall and Warren, 1984)
We found that outer membrane vesicles (OMVs) derived from H. pylori 7.13 showed protective activity in mice without significant toxicity (Liu et al, 2019).These studies suggest H. pylori OMVs can be used as adjuvant candidates
We found that the immune response to 200 μg outer membrane proteins (OMPs) was slightly weaker than to whole cell vaccine (WCV), this difference was not significant (Figure 2)
Summary
Helicobacter pylori (H. pylori), a gram-negative bacterium colonizing the mucus layer over the gastric epithelium, has been implicated in the pathogenesis of chronic gastritis and peptic ulcer (Marshall and Warren, 1984). Antibiotic combination therapy, proton pump inhibitor (PPI)-based triple therapy or bismuth-containing quadruple therapy (BQT) are currently used as prevalent and efficient treatments to eradicate the colonization of H. pylori (Hu et al, 2020). H. pylori OMVs as Adjuvants Promote Protective Efficacy levofloxacin, has significantly increased globally (Smith et al, 2019). To determine other effective treatments against H. pylori infection, many studies have focused on selecting improved vaccine candidates, including whole cell vaccine (WCV), proteinbased vaccine, and synthetic carbohydrate vaccines, etc. Our research group focused on the outer membrane vesicles (OMVs), a natural secretion of gram-negative bacteria, to assess its potential as a potent immunogen for clinical use. Previous results indicated good performance of OMVs in animal studies, when either utilized as a vaccine or adjuvant (Tan et al, 2018; Liu et al, 2019)
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