A bacterial outer membrane vesicle-based click vaccine elicits potent immune response against Staphylococcus aureus in mice

Staphylococcus aureus infection is a severe public health concern with the growing number of multidrug-resistant strains. S. aureus can circumvent the defense mechanisms of host immunity with the aid of multiple virulence factors. An efficacious multicomponent vaccine targeting diverse immune evasio...

Full description

Bibliographic Details
Main Authors: Jingjing Sun, Xuansheng Lin, Yige He, Baozhong Zhang, Nan Zhou, Jian-dong Huang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1088501/full
_version_ 1797948189301538816
author Jingjing Sun
Jingjing Sun
Xuansheng Lin
Yige He
Yige He
Baozhong Zhang
Nan Zhou
Nan Zhou
Jian-dong Huang
Jian-dong Huang
Jian-dong Huang
Jian-dong Huang
author_facet Jingjing Sun
Jingjing Sun
Xuansheng Lin
Yige He
Yige He
Baozhong Zhang
Nan Zhou
Nan Zhou
Jian-dong Huang
Jian-dong Huang
Jian-dong Huang
Jian-dong Huang
author_sort Jingjing Sun
collection DOAJ
description Staphylococcus aureus infection is a severe public health concern with the growing number of multidrug-resistant strains. S. aureus can circumvent the defense mechanisms of host immunity with the aid of multiple virulence factors. An efficacious multicomponent vaccine targeting diverse immune evasion strategies developed by S. aureus is thus crucial for its infection control. In this study, we exploited the SpyCatcher-SpyTag system to engineer bacterial outer membrane vesicles (OMVs) for the development of a multitargeting S. aureus click vaccine. We decorated OMVs with surface exposed SpyCatcher via a truncated OmpA(a.a 1-155)-SpyCatcher fusion. The engineered OMVs can flexibly bind with various SpyTag-fused S. aureus antigens to generate an OMV-based click vaccine. Compared with antigens mixed with alum adjuvant, the click vaccine simultaneously induced more potent antigen-specific humoral and Th1-based cellular immune response, which afforded protection against S. aureus Newman lethal challenge in a mouse model. Our study provided a flexible and versatile click vaccine strategy with the potential for fighting against emerging S. aureus clinical isolates.
first_indexed 2024-04-10T21:40:32Z
format Article
id doaj.art-9582ad7051174ce2b48e8b055f610848
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-04-10T21:40:32Z
publishDate 2023-01-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj.art-9582ad7051174ce2b48e8b055f6108482023-01-19T05:59:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011410.3389/fimmu.2023.10885011088501A bacterial outer membrane vesicle-based click vaccine elicits potent immune response against Staphylococcus aureus in miceJingjing Sun0Jingjing Sun1Xuansheng Lin2Yige He3Yige He4Baozhong Zhang5Nan Zhou6Nan Zhou7Jian-dong Huang8Jian-dong Huang9Jian-dong Huang10Jian-dong Huang11CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, ChinaZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, ChinaSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaCAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, ChinaSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaCAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, ChinaCAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, ChinaZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, ChinaCAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, ChinaSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Clinical Oncology, Shenzhen Key Laboratory for Cancer Metastasis and Personalized Therapy, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, ChinaGuangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen University, Guangzhou, ChinaStaphylococcus aureus infection is a severe public health concern with the growing number of multidrug-resistant strains. S. aureus can circumvent the defense mechanisms of host immunity with the aid of multiple virulence factors. An efficacious multicomponent vaccine targeting diverse immune evasion strategies developed by S. aureus is thus crucial for its infection control. In this study, we exploited the SpyCatcher-SpyTag system to engineer bacterial outer membrane vesicles (OMVs) for the development of a multitargeting S. aureus click vaccine. We decorated OMVs with surface exposed SpyCatcher via a truncated OmpA(a.a 1-155)-SpyCatcher fusion. The engineered OMVs can flexibly bind with various SpyTag-fused S. aureus antigens to generate an OMV-based click vaccine. Compared with antigens mixed with alum adjuvant, the click vaccine simultaneously induced more potent antigen-specific humoral and Th1-based cellular immune response, which afforded protection against S. aureus Newman lethal challenge in a mouse model. Our study provided a flexible and versatile click vaccine strategy with the potential for fighting against emerging S. aureus clinical isolates.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1088501/fullouter membrane vesiclesStaphylococcus aureus vaccineSpyCatcher-SpyTag‘click’ displayflexible antigen displaymulti-targeting vaccine
spellingShingle Jingjing Sun
Jingjing Sun
Xuansheng Lin
Yige He
Yige He
Baozhong Zhang
Nan Zhou
Nan Zhou
Jian-dong Huang
Jian-dong Huang
Jian-dong Huang
Jian-dong Huang
A bacterial outer membrane vesicle-based click vaccine elicits potent immune response against Staphylococcus aureus in mice
Frontiers in Immunology
outer membrane vesicles
Staphylococcus aureus vaccine
SpyCatcher-SpyTag
‘click’ display
flexible antigen display
multi-targeting vaccine
title A bacterial outer membrane vesicle-based click vaccine elicits potent immune response against Staphylococcus aureus in mice
title_full A bacterial outer membrane vesicle-based click vaccine elicits potent immune response against Staphylococcus aureus in mice
title_fullStr A bacterial outer membrane vesicle-based click vaccine elicits potent immune response against Staphylococcus aureus in mice
title_full_unstemmed A bacterial outer membrane vesicle-based click vaccine elicits potent immune response against Staphylococcus aureus in mice
title_short A bacterial outer membrane vesicle-based click vaccine elicits potent immune response against Staphylococcus aureus in mice
title_sort bacterial outer membrane vesicle based click vaccine elicits potent immune response against staphylococcus aureus in mice
topic outer membrane vesicles
Staphylococcus aureus vaccine
SpyCatcher-SpyTag
‘click’ display
flexible antigen display
multi-targeting vaccine
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1088501/full
work_keys_str_mv AT jingjingsun abacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT jingjingsun abacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT xuanshenglin abacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT yigehe abacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT yigehe abacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT baozhongzhang abacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT nanzhou abacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT nanzhou abacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT jiandonghuang abacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT jiandonghuang abacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT jiandonghuang abacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT jiandonghuang abacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT jingjingsun bacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT jingjingsun bacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT xuanshenglin bacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT yigehe bacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT yigehe bacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT baozhongzhang bacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT nanzhou bacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT nanzhou bacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT jiandonghuang bacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT jiandonghuang bacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT jiandonghuang bacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice
AT jiandonghuang bacterialoutermembranevesiclebasedclickvaccineelicitspotentimmuneresponseagainststaphylococcusaureusinmice