Surface Display of Type 1 Fimbriae on <i>Shigella flexneri</i> Induces Antigen-Specific Immune Response via Oral Route
Background: Live attenuated bacteria are promising candidates for mucosal vaccine delivery due to their ability to elicit robust immune responses. FimH is the adhesion protein of type 1 fimbriae, which is used as mucosal adjuvants. This study aims to develop a novel attenuated live bacterial vector...
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MDPI AG
2025-03-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/13/3/280 |
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| author | Shuli Sang Rui Yu Yunyun Mao Yanfang Zhai Chen Cao Kai Li Yiyan Guan Haoxia Tao Chunjie Liu Yanchun Wang |
| author_facet | Shuli Sang Rui Yu Yunyun Mao Yanfang Zhai Chen Cao Kai Li Yiyan Guan Haoxia Tao Chunjie Liu Yanchun Wang |
| author_sort | Shuli Sang |
| collection | DOAJ |
| description | Background: Live attenuated bacteria are promising candidates for mucosal vaccine delivery due to their ability to elicit robust immune responses. FimH is the adhesion protein of type 1 fimbriae, which is used as mucosal adjuvants. This study aims to develop a novel attenuated live bacterial vector via fimbriae recovery on <i>Shigella flexneri.</i> Methods: We generated pBAD-Fim/FWL01 by deleting IS elements in the fimbrial cluster of <i>S. flexneri</i> 2a strain T32. Transmission electron microscopy (TEM) and a mannose–sensitive agglutination assay were used to confirm that type 1 fimbriae were displayed on the recombinant strain. We then evaluated the immune induction of pBAD-Fim/FWL01 in J774A.1 murine macrophages and mice. Additionally, we used pBAD-Fim/FWL01 to deliver the neutrophil–activating protein A subunit (NapA) to assess immunogenicity. Results: Functional type 1 fimbriae on pBAD-Fim/FWL01 were confirmed using TEM and mannose–sensitive agglutination assays. Transcriptome analysis, qRT-PCR, and ELISA assays revealed that pBAD-Fim/FWL01 significantly stimulated mouse macrophages to release cytokines IL-1α, IL-1β, IL-6, and IL-10, inducing an immune response. Orally administrated pBAD-Fim-trc-napA-His/FWL01 elicited significant mucosal and humoral immune responses. Conclusions: The strain pBAD-Fim/FWL01, which expresses type 1 fimbriae, holds promise for development as an attenuated bacterial vaccine vehicle. |
| format | Article |
| id | doaj-art-eac4bf202ff74837a335d380ca83d27b |
| institution | DOAJ |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-eac4bf202ff74837a335d380ca83d27b2025-08-20T02:43:10ZengMDPI AGVaccines2076-393X2025-03-0113328010.3390/vaccines13030280Surface Display of Type 1 Fimbriae on <i>Shigella flexneri</i> Induces Antigen-Specific Immune Response via Oral RouteShuli Sang0Rui Yu1Yunyun Mao2Yanfang Zhai3Chen Cao4Kai Li5Yiyan Guan6Haoxia Tao7Chunjie Liu8Yanchun Wang9Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, 20 Dongda Street, Fengtai District, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, 20 Dongda Street, Fengtai District, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, 20 Dongda Street, Fengtai District, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, 20 Dongda Street, Fengtai District, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, 20 Dongda Street, Fengtai District, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, 20 Dongda Street, Fengtai District, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, 20 Dongda Street, Fengtai District, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, 20 Dongda Street, Fengtai District, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, 20 Dongda Street, Fengtai District, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, 20 Dongda Street, Fengtai District, Beijing 100071, ChinaBackground: Live attenuated bacteria are promising candidates for mucosal vaccine delivery due to their ability to elicit robust immune responses. FimH is the adhesion protein of type 1 fimbriae, which is used as mucosal adjuvants. This study aims to develop a novel attenuated live bacterial vector via fimbriae recovery on <i>Shigella flexneri.</i> Methods: We generated pBAD-Fim/FWL01 by deleting IS elements in the fimbrial cluster of <i>S. flexneri</i> 2a strain T32. Transmission electron microscopy (TEM) and a mannose–sensitive agglutination assay were used to confirm that type 1 fimbriae were displayed on the recombinant strain. We then evaluated the immune induction of pBAD-Fim/FWL01 in J774A.1 murine macrophages and mice. Additionally, we used pBAD-Fim/FWL01 to deliver the neutrophil–activating protein A subunit (NapA) to assess immunogenicity. Results: Functional type 1 fimbriae on pBAD-Fim/FWL01 were confirmed using TEM and mannose–sensitive agglutination assays. Transcriptome analysis, qRT-PCR, and ELISA assays revealed that pBAD-Fim/FWL01 significantly stimulated mouse macrophages to release cytokines IL-1α, IL-1β, IL-6, and IL-10, inducing an immune response. Orally administrated pBAD-Fim-trc-napA-His/FWL01 elicited significant mucosal and humoral immune responses. Conclusions: The strain pBAD-Fim/FWL01, which expresses type 1 fimbriae, holds promise for development as an attenuated bacterial vaccine vehicle.https://www.mdpi.com/2076-393X/13/3/280type 1 fimbriaeattenuated bacterial vector<i>Shigella flexneri</i> |
| spellingShingle | Shuli Sang Rui Yu Yunyun Mao Yanfang Zhai Chen Cao Kai Li Yiyan Guan Haoxia Tao Chunjie Liu Yanchun Wang Surface Display of Type 1 Fimbriae on <i>Shigella flexneri</i> Induces Antigen-Specific Immune Response via Oral Route Vaccines type 1 fimbriae attenuated bacterial vector <i>Shigella flexneri</i> |
| title | Surface Display of Type 1 Fimbriae on <i>Shigella flexneri</i> Induces Antigen-Specific Immune Response via Oral Route |
| title_full | Surface Display of Type 1 Fimbriae on <i>Shigella flexneri</i> Induces Antigen-Specific Immune Response via Oral Route |
| title_fullStr | Surface Display of Type 1 Fimbriae on <i>Shigella flexneri</i> Induces Antigen-Specific Immune Response via Oral Route |
| title_full_unstemmed | Surface Display of Type 1 Fimbriae on <i>Shigella flexneri</i> Induces Antigen-Specific Immune Response via Oral Route |
| title_short | Surface Display of Type 1 Fimbriae on <i>Shigella flexneri</i> Induces Antigen-Specific Immune Response via Oral Route |
| title_sort | surface display of type 1 fimbriae on i shigella flexneri i induces antigen specific immune response via oral route |
| topic | type 1 fimbriae attenuated bacterial vector <i>Shigella flexneri</i> |
| url | https://www.mdpi.com/2076-393X/13/3/280 |
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