Oral Administration of a Shigella 2aT32-Based Vaccine Expressing UreB-HspA Fusion Antigen With and Without Parenteral rUreB-HspA Boost Confers Protection Against Helicobacter pylori in Mice Model

Abstract

Helicobacter pylori (H. pylori) is a gram-negative pathogen classified as a class I carcinogen. The H. pylori urease B subunit (UreB) and heat shock protein A (HspA) are two important vaccine candidate antigens. In this study, we evaluated the immunogenicity and immunoprotective effect of the attenuated Shigella vector vaccine SH02 expressing the UreB-HspA fusion protein of H. pylori in a mouse model. Oral SH02 with or without subcutaneous injection of rUreB-HspA induced antigen-specific serum IgG, mucosal sIgA, and T cells immune response. Subcutaneous injection of the candidate antigen rUreB-HspA enhanced the level of serum antigen-specific IgG antibodies (p < 0.0001) and the levels of IgG1/IgG2a/IgG2b subtypes. In addition, injection boost also increased the proportion of spleen antigen-specific CD4+CD154+ T cells (p < 0.001), and the proportion of CD4+CD154+ T cells that secrete IFN-γ and IL-17A. Following the H. pylori challenge, the levels of H. pylori colonization in the two experimental groups (Groups A and B) significantly reduced compared with the control group (p < 0.001), indicating that the candidate vaccine yielded a preventive effect of anti-H.pylori infection. Compared with the non-subcutaneous booster injection group (Group A), the subcutaneous booster injection group (Group B) exhibited less gastric inflammation, but there was no significant difference in the level of colonization (p > 0.05). These results lay a foundation for the development of a vaccine against H. pylori and the optimization of immunization methods and procedures to prevent H. pylori infection.

Outer membrane vesicles from genetically engineered Salmonella enterica serovar Typhimurium presenting Helicobacter pylori antigens UreB and CagA induce protection against Helicobacter pylori infection in mice

“…Typhimurium Δ rfbP Δ fliC Δ fljB Δ ompA mutant strain successfully elicited strong humoral and mucosal immunity in mice, and markedly increased IgG and IgA levels. IFN-γ and IL-17 have been proven to be vital in immunity against H. pylori infection [ 24 ], and CD154 expression on the surface of activated CD4 + T cells determines the degree of differentiation of CD4 + T cells into Th1 and Th17 cells after immunization [ 25 ]. Our data showed that the constructed vaccine induced significant increases in CD4 + T cells relevant to preventing H. pylori infection and related cytokines IFN-γ and IL-17 levels.…”

Inhalable vaccine of bacterial culture supernatant extract mediates protection against fatal pulmonary anthrax

“…A lymphocyte proliferation assay was conducted according to the revised version of a previously method [ 25 , 26 ]. Single-cell suspensions (4 × 10 5 /well) were seeded in plates containing RPMI 1640 medium containing 10% (v/v) fetal bovine serum, 1% (v/v) penicillin–streptomycin (Thermo Fisher Scientific), and 20 µg/mL rPA at 37 °C and under 5% CO 2 for 72 h. During the final four hours of incubation, 20 µL CCK-8 solution was added.…”

Novel therapeutic regimens against Helicobacter pylori: an updated systematic review

“…The basic immunization consisted of either three oral administrations or two oral immunizations, followed by a third immunization involving a subcutaneous injection of rUreB-HspA for immune enhancement. Both approaches significantly reduced H. pylori colonization and gastric inflammation in mice ( Zhang et al, 2022 ).…”