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.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	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.
Συγγραφείς:	Liu Q; The First Affiliated Hospital, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University., Shang Y; The First Affiliated Hospital, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University., Shen L; The First Affiliated Hospital, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University., Yu X; The First Affiliated Hospital, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University., Cao Y; The First Affiliated Hospital, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University., Zeng L; The First Affiliated Hospital, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University., Zhang H; The First Affiliated Hospital, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University.; The Second Clinical Medical College, Nanchang University, Nanchang, China., Rao Z; The First Affiliated Hospital, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University.; HuanKui Academy, Nanchang University, Nanchang, China., Li Y; The First Affiliated Hospital, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University.; The First Clinical Medical College, Nanchang University, Nanchang, China., Tao Z; The First Affiliated Hospital, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University., Liu Z; The First Affiliated Hospital, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University.; HuanKui Academy, Nanchang University, Nanchang, China., Huang X; The First Affiliated Hospital, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University.
Πηγή:	Virulence [Virulence] 2024 Dec; Vol. 15 (1), pp. 2367783. Date of Electronic Publication: 2024 Jun 27.
Τύπος έκδοσης:	Journal Article; Research Support, Non-U.S. Gov't
Γλώσσα:	English
Στοιχεία περιοδικού:	Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101531386 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-5608 (Electronic) Linking ISSN: 21505594 NLM ISO Abbreviation: Virulence Subsets: MEDLINE
Imprint Name(s):	Publication: 2015- : Philadelphia, PA : Taylor & Francis Original Publication: Austin, Tex. : Landes Bioscience
Ιατρικοί όροι (MeSH):	Helicobacter Infections/prevention & control , Helicobacter Infections/immunology , Helicobacter Infections/microbiology , Bacterial Proteins/genetics , Bacterial Proteins/immunology , Helicobacter pylori/immunology , Helicobacter pylori/genetics , Salmonella typhimurium/immunology , Salmonella typhimurium/genetics , Antigens, Bacterial/immunology , Antigens, Bacterial*/genetics, Bacterial Vaccines/immunology ; Bacterial Vaccines/genetics ; Antibodies, Bacterial/immunology ; Antibodies, Bacterial/blood ; Urease/immunology ; Urease/genetics ; Animals ; Mice ; Female ; Immunoglobulin G ; Genetic Engineering ; Disease Models, Animal
Περίληψη:	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.
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Contributed Indexing:	Keywords: Helicobacter pylori; autotransporter system; outer membrane vesicles; vaccine platform Local Abstract: [plain-language-summary] Outer membrane vesicles (OMVs), as a novel antigen delivery platform, has been used in vaccine design for various pathogens and even tumors. Salmonella enterica serovar Typhimurium (S. 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 Escherichia coli. This study focuses on the design of Helicobacter pylori ;(H. pylori) vaccines, utilizing genetically modified Salmonella OMVs to present several major antigens of H. pylori, including UreB, VacA and CagA. The optimal Salmonella OMV delivery vector and antigen combinations are screened and identified, providing new ideas for the development of H. pylori vaccines and an integrated antigen delivery platform for other difficult to develop vaccines for bacteria, viruses, and even tumors.
Molecular Sequence:	figshare 10.6084/m9.figshare.25670886
Substance Nomenclature:	0 (Bacterial Proteins) 0 (Antigens, Bacterial) 0 (cagA protein, Helicobacter pylori) 0 (Bacterial Vaccines) 0 (Antibodies, Bacterial) 0 (Immunoglobulin G) EC 3.5.1.5 (Urease)
Entry Date(s):	Date Created: 20240628 Date Completed: 20240628 Latest Revision: 20250416
Update Code:	20260130
PubMed Central ID:	PMC11216100
DOI:	10.1080/21505594.2024.2367783
PMID:	38937901
Βάση Δεδομένων:	MEDLINE

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ISSN:	2150-5608
DOI:	10.1080/21505594.2024.2367783