Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infection

Abstract Background Helicobacter pylori (H. pylori) causes chronic gastric disease. An efficient oral vaccine would be mucosa-targeted and offer defense against colonization of invasive infection in the digestive system. Proteolytic enzymes and acidic environment in the gastrointestinal tract (GT) c...

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Main Authors: Furui Zhang, Linhan Ni, Zhen Zhang, Xuegang Luo, Xuequan Wang, Wenmiao Zhou, Jiale Chen, Jing Liu, Yuliang Qu, Kunmei Liu, Le Guo
Format: Article
Language:English
Published: BMC 2024-02-01
Series:Microbial Cell Factories
Subjects:
Online Access:https://doi.org/10.1186/s12934-024-02321-4
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author Furui Zhang
Linhan Ni
Zhen Zhang
Xuegang Luo
Xuequan Wang
Wenmiao Zhou
Jiale Chen
Jing Liu
Yuliang Qu
Kunmei Liu
Le Guo
author_facet Furui Zhang
Linhan Ni
Zhen Zhang
Xuegang Luo
Xuequan Wang
Wenmiao Zhou
Jiale Chen
Jing Liu
Yuliang Qu
Kunmei Liu
Le Guo
author_sort Furui Zhang
collection DOAJ
description Abstract Background Helicobacter pylori (H. pylori) causes chronic gastric disease. An efficient oral vaccine would be mucosa-targeted and offer defense against colonization of invasive infection in the digestive system. Proteolytic enzymes and acidic environment in the gastrointestinal tract (GT) can, however, reduce the effectiveness of oral vaccinations. For the creation of an edible vaccine, L. lactis has been proposed as a means of delivering vaccine antigens. Results We developed a plSAM (pNZ8148-SAM) that expresses a multiepitope vaccine antigen SAM-WAE containing Urease, HpaA, HSP60, and NAP extracellularly (named LL-plSAM-WAE) to increase the efficacy of oral vaccinations. We then investigated the immunogenicity of LL-plSAM-WAE in Balb/c mice. Mice that received LL-plSAM-WAE or SAM-WAE with adjuvant showed increased levels of antibodies against H. pylori, including IgG and sIgA, and resulted in significant reductions in H. pylori colonization. Furthermore, we show that SAM-WAE and LL-plSAM-WAE improved the capacity to target the vaccine to M cells. Conclusions These findings suggest that recombinant L. lactis could be a promising oral mucosa vaccination for preventing H. pylori infection.
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spelling doaj.art-86fe6f133ca240efbc904fc4c56f406a2024-03-06T08:06:38ZengBMCMicrobial Cell Factories1475-28592024-02-0123111510.1186/s12934-024-02321-4Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infectionFurui Zhang0Linhan Ni1Zhen Zhang2Xuegang Luo3Xuequan Wang4Wenmiao Zhou5Jiale Chen6Jing Liu7Yuliang Qu8Kunmei Liu9Le Guo10College of First Clinical Medicine, Ningxia Medical UniversityCollege of Pharmacy, Ningxia Medical UniversityDepartment of Geriatrics and Special Needs Medicine, General Hospital of Ningxia Medical UniversityKey Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, College of Biotechnology, Tianjin University of Science and TechnologyKey Laboratory of Radiation Oncology of Taizhou, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical UniversityCollege of First Clinical Medicine, Ningxia Medical UniversityCollege of First Clinical Medicine, Ningxia Medical UniversityCollege of Laboratory Medicine , Ningxia Medical UniversityCollege of Laboratory Medicine , Ningxia Medical UniversityCollege of Pharmacy, Ningxia Medical UniversityCollege of First Clinical Medicine, Ningxia Medical UniversityAbstract Background Helicobacter pylori (H. pylori) causes chronic gastric disease. An efficient oral vaccine would be mucosa-targeted and offer defense against colonization of invasive infection in the digestive system. Proteolytic enzymes and acidic environment in the gastrointestinal tract (GT) can, however, reduce the effectiveness of oral vaccinations. For the creation of an edible vaccine, L. lactis has been proposed as a means of delivering vaccine antigens. Results We developed a plSAM (pNZ8148-SAM) that expresses a multiepitope vaccine antigen SAM-WAE containing Urease, HpaA, HSP60, and NAP extracellularly (named LL-plSAM-WAE) to increase the efficacy of oral vaccinations. We then investigated the immunogenicity of LL-plSAM-WAE in Balb/c mice. Mice that received LL-plSAM-WAE or SAM-WAE with adjuvant showed increased levels of antibodies against H. pylori, including IgG and sIgA, and resulted in significant reductions in H. pylori colonization. Furthermore, we show that SAM-WAE and LL-plSAM-WAE improved the capacity to target the vaccine to M cells. Conclusions These findings suggest that recombinant L. lactis could be a promising oral mucosa vaccination for preventing H. pylori infection.https://doi.org/10.1186/s12934-024-02321-4Helicobacter pyloriLactic acid bacteriaM cell-targetingVaccine delivery systemMucosal immune response
spellingShingle Furui Zhang
Linhan Ni
Zhen Zhang
Xuegang Luo
Xuequan Wang
Wenmiao Zhou
Jiale Chen
Jing Liu
Yuliang Qu
Kunmei Liu
Le Guo
Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infection
Microbial Cell Factories
Helicobacter pylori
Lactic acid bacteria
M cell-targeting
Vaccine delivery system
Mucosal immune response
title Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infection
title_full Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infection
title_fullStr Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infection
title_full_unstemmed Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infection
title_short Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infection
title_sort recombinant l lactis vaccine ll plsam wae targeting four virulence factors provides mucosal immunity against h pylori infection
topic Helicobacter pylori
Lactic acid bacteria
M cell-targeting
Vaccine delivery system
Mucosal immune response
url https://doi.org/10.1186/s12934-024-02321-4
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