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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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
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| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/13/3/280 |
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| Summary: | 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. |
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| ISSN: | 2076-393X |