Orally-administered outer-membrane vesicles fromHelicobacter pylorireduceH. pyloriinfection via Th2-biased immune responses in mice

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.

Outer Membrane Vesicles From Brucella melitensis Modulate Immune Response and Induce Cytoskeleton Rearrangement in Peripheral Blood Mononuclear Cells

“…OMVs purified from Aeromonas hydrophila induced the expression of the surface activation marker CD69 in B and T lymphocytes in vitro (Avila-Calderón et al, 2018). On the other hand, OMVs have been used as an in vivo vaccine, inducing protection in mice after exposing them with the virulent strain as observed in OMVs from Acinetobacter baumannii, Helicobacter pylori, Escherichia coli, and Brucella (Avila-Calderón et al, 2012;Araiza-Villanueva et al, 2019;Liu et al, 2019;Wang et al, 2019;Pulido et al, 2020).…”

Development of Different Methods for Preparing Acinetobacter baumannii Outer Membrane Vesicles Vaccine: Impact of Preparation Method on Protective Efficacy

“…The licensed MenB OMV vaccines induce a protective immune response and have been proven effective in controlling local epidemic outbreaks. OMV vaccines had also been developed to combat infectious diseases caused by other pathogens in animal models, such as Helicobacter pylori(42), Pseudomonas aeruginosa (43), Escherichia coli(44), and Streptococcus pneumonia(45), which offered attractive strategies for protection against bacterial infection.…”

Naturally secreted bacterial outer membrane vesicles: potential platform for a vaccine againstCampylobacter jejuni

“…The consistent and steady rise of IgG in the serum with balanced antibody isotypic profiles in mice mucosally administered with OMVs indicate mixed Th1/Th2 type responses, which could possibly be due to the intrinsic property of the proteins associated with OMVs as well as the adjuvant effect of CS [72–74]. However, it is not clear how mucosal administration of OMVs affects the systemic antibody responses; one possible reason could be systemic migration of antigen primed local B cells present in the gut-associated lymphoid tissue (GALT) via lymphatic circulation [14,75–77]. Since pathogen-specific expansion and contraction of immune cells are the hallmarks of the effective activation of the immune system [78,79], we evaluated the priming effects of OMVs immunization by systematic analysis of cell proliferation, ability to produce nitric oxide (NO), expression of cytokine genes, and finally immunophenotypic profile of T cells [19,44,80–82].…”