{"title":"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.","authors":"Qiong Liu, Yinpan Shang, Lu Shen, Xiaomin Yu, Yanli Cao, Lingbing Zeng, Hanchi Zhang, Zirong Rao, Yi Li, Ziwei Tao, Zhili Liu, Xiaotian Huang","doi":"10.1080/21505594.2024.2367783","DOIUrl":null,"url":null,"abstract":"<p><p><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.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.5000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216100/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virulence","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/21505594.2024.2367783","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/27 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Helicobacter pylori 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 H. pylori colonization. However, while current strategies prefer to formulate vaccines with a single H. pylori 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 H. pylori antigen proteins (UreB, CagA, and VacA) onto the surface of OMVs derived from Salmonella enterica serovar Typhimurium (S. Typhimurium) mutant strains using the hemoglobin protease (Hbp) autotransporter system. In various knockout strategies, we found that OMVs isolated from the ΔrfbP ΔfliC ΔfljB ΔompA 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 H. pylori. Next, OMVs derived from ΔrfbP ΔfliC ΔfljB ΔompA mutants were used as a vector to deliver different combinations of H. pylori antigens. The antibody and cytokine levels and challenge experiments in mice model indicated that co-delivering UreB and CagA could protect against H. pylori and antigen-specific T cell responses. In summary, OMVs derived from the S. Typhimurium ΔrfbP ΔfliC ΔfljB ΔompA mutant strain as the vector while importing H. pylori UreB and CagA as antigenic proteins using the Hbp autotransporter system would greatly benefit controlling H. pylori infection.
期刊介绍:
Virulence is a fully open access peer-reviewed journal. All articles will (if accepted) be available for anyone to read anywhere, at any time immediately on publication.
Virulence is the first international peer-reviewed journal of its kind to focus exclusively on microbial pathogenicity, the infection process and host-pathogen interactions. To address the new infectious challenges, emerging infectious agents and antimicrobial resistance, there is a clear need for interdisciplinary research.