Outer membrane vesicles from genetically engineered <i>Salmonella enterica</i> serovar Typhimurium presenting <i>Helicobacter pylori</i> antigens UreB and CagA induce protection against <i>Helicobacter pylori</i> infection in mice
Creators: name: Liu, Qiong
name: Shang, Yinpan
name: Shen, Lu
name: Yu, Xiaomin
name: Cao, Yanli
name: Zeng, Lingbing
name: Zhang, Hanchi
name: Rao, Zirong
name: Li, Yi
name: Tao, Ziwei
name: Liu, Zhili
name: Huang, Xiaotian
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Space Science
subject: Microbiology
subject: FOS: Biological sciences
subject: Biotechnology
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology

description: <i>Helicobacter pylori</i> causes globally prevalent infections that are highly related to chronic gastritis and even development of gastric carcinomas. With the increase of antibiotic resistance, scientists have begun to search for better vaccine design strategies to eradicate <i>H. pylori</i> colonization. However, while current strategies prefer to formulate vaccines with a single <i>H. pylori</i> antigen, their potential has not yet been fully realized. Outer membrane vesicles (OMVs) are a potential platform since they could deliver multiple antigens. In this study, we engineered three crucial <i>H. pylori</i> antigen proteins (UreB, CagA, and VacA) onto the surface of OMVs derived from <i>Salmonella enterica</i> serovar Typhimurium (<i>S</i>. Typhimurium) mutant strains using the hemoglobin protease (Hbp) autotransporter system. In various knockout strategies, we found that OMVs isolated from the Δ<i>rfbP</i> Δ<i>fliC</i> Δ<i>fljB</i> Δ<i>ompA</i> mutants could cause distinct increases in immunoglobulin G (IgG) and A (IgA) levels and effectively trigger T helper 1- and 17-biased cellular immune responses, which perform a vital role in protecting against <i>H. pylori</i>. Next, OMVs derived from Δ<i>rfbP</i> Δ<i>fliC</i> Δ<i>fljB</i> Δ<i>ompA</i> mutants were used as a vector to deliver different combinations of <i>H. pylori</i> antigens. The antibody and cytokine levels and challenge experiments in mice model indicated that co-delivering UreB and CagA could protect against <i>H. pylori</i> and antigen-specific T cell responses. In summary, OMVs derived from the <i>S</i>. Typhimurium Δ<i>rfbP</i> Δ<i>fliC</i> Δ<i>fljB</i> Δ<i>ompA</i> mutant strain as the vector while importing <i>H. pylori</i> UreB and CagA as antigenic proteins using the Hbp autotransporter system would greatly benefit controlling <i>H. pylori</i> infection. Outer membrane vesicles (OMVs), as a novel antigen delivery platform, has been used in vaccine design for various pathogens and even tumors. <i>Salmonella enterica</i> serovar Typhimurium (<i>S</i>. Typhimurium), as a bacterium that is easy to engineer and has both adjuvant efficacy and immune stimulation capacity, has become the preferred bacterial vector for purifying OMVs after <i>Escherichia coli</i>. This study focuses on the design of <i>Helicobacter pylori</i> ;(<i>H. pylori</i>) vaccines, utilizing genetically modified <i>Salmonella</i> OMVs to present several major antigens of <i>H. pylori</i>, including UreB, VacA and CagA. The optimal <i>Salmonella</i> OMV delivery vector and antigen combinations are screened and identified, providing new ideas for the development of <i>H. pylori</i> vaccines and an integrated antigen delivery platform for other difficult to develop vaccines for bacteria, viruses, and even tumors.