Outer Membrane Vesicles of Helicobacter pylori 7.13 as Adjuvants Promote Protective Efficacy Against Helicobacter pylori Infection

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.

Outer Membrane Vesicle Production by Helicobacter pylori Represents an Approach for the Delivery of Virulence Factors CagA, VacA and UreA into Human Gastric Adenocarcinoma (AGS) Cells

“…OMVs from H. pylori 7.13 strain were found to induce immune responses in mice without causing mucosal inflammation [ 52 ]. Using H. pylori 7.13 OMVs as adjuvants with a vaccine derived from outer membrane proteins or whole cell vaccine also significantly improved the protective effect in immunized mice [ 53 ]. Notably, LPS or other lipids in OMVs might not have the immunostimulatory role while H. pylori 7.13 OMVs were applied as adjuvants [ 53 ].…”

“…Using H. pylori 7.13 OMVs as adjuvants with a vaccine derived from outer membrane proteins or whole cell vaccine also significantly improved the protective effect in immunized mice [ 53 ]. Notably, LPS or other lipids in OMVs might not have the immunostimulatory role while H. pylori 7.13 OMVs were applied as adjuvants [ 53 ]. Lipoprotein 20 (Lpp20) located on the surface of H. pylori OMVs was previously identified as a vaccine candidate which elicited a strong immune response in mice and the antibody against Lpp20 effectively lowered the colonization of H. pylori SS1 strain [ 54 , 55 ].…”

A Polypeptide of Tumor-Associated Antigen L6 with Intrinsic Adjuvant Activity Enhances Antitumor Immunity

“…Bacterial components, such as cholera toxin and E. coli heat-labile enterotoxin, can also be used as adjuvants to boost the mucosal vaccination against H. pylori in mice [ 33 ], but enterotoxicity limits their clinical applications. Outer membrane vesicles of H. pylori were reported as non-toxic adjuvants to induce long-term protection with humoral and Th-1 immunity against H. pylori in mice [ 34 ]. Lipids are one component of the outer membrane vesicles of Gram-negative bacteria, and play roles in immune regulation [ 35 ].…”

Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

“…The analysis demonstrated that vaccines with H. pylori -OMVs induced a Th2 and Th17 biased immunity, increasing cell mediated and humoral immunity, which reduces H. pylori colonization in a mouse model. Consequently, H. pylori -OMVs are effective adjuvants for these types of vaccines [ 180 ].…”