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- Published: 22 November 2025
Nature Communications , Article number: (2025) Cite this article
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Abstract
Oral vaccines provide a non-invasive approach for cancer immunotherapy but face challenges in gastrointestinal stability, antigen presentation, and mucosal delivery. Here, we present an engineered probiotic-based oral vaccine system, BacOR-Fn-…
- Article
- Open access
- Published: 22 November 2025
Nature Communications , Article number: (2025) Cite this article
We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.
Abstract
Oral vaccines provide a non-invasive approach for cancer immunotherapy but face challenges in gastrointestinal stability, antigen presentation, and mucosal delivery. Here, we present an engineered probiotic-based oral vaccine system, BacOR-Fn-T+phiX174, featuring genetically encoded dual-antigen ferritin arrays and inducible bacterial lysis. Upon oral administration and arabinose induction, the probiotic strain lyses in situ, releasing OVA/TRP2-decorated ferritin nanoparticles that efficiently traverse the intestinal barrier via M-cell targeting and activate mucosal dendritic cells. This platform robustly stimulates CD8+ and CD4+ T-cell responses, enhances B-cell and macrophage activation, reduces regulatory T cells, and provides therapeutic efficacy against melanoma in both lung metastasis and subcutaneous tumor models. It also establishes durable immunological memory without disrupting systemic or mucosal homeostasis. This work offers a programmable bacterial chassis for precise antigen array presentation and controlled delivery, representing a promising strategy for next-generation, needle-free cancer vaccines.
Data availability
Data supporting the findings of this work are available within the paper and its Supplementary Information files. Source data are available for Figs. 2–8 and Supplementary Figs. 2, 3, 5, 7, 8, 9, 10, 14, 22, 29, 30, and 32 in the associated source data file. Source data are provided with this paper.
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Acknowledgements
This work was supported by the National Nature Science Foundation of China (Nos. 32301187, Y.Y. and 32000996, B.J.) and the Henan Province Excellent Youth Science Foundation (no. 252300421143, Y.Y.), the Key Program of Nanozyme Laboratory in Zhongyuan (NLZ-KP2024NIC02, B.J.), the Henan AIMS Professional Development Fund (JBKY250304, B.J.), and the Grant for International Joint Research Project of the Institute of Medical Science, the University of Tokyo (no. Extension-2019-K3005, X.Y.).
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Author notes
These authors contributed equally: Yale Yue, Qi Xin.
Authors and Affiliations
Nanozyme Laboratory in Zhongyuan, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
Yale Yue, Yuanyuan Zhu, Dandan Zhu, Baohua Zhang, Xiyun Yan & Bing Jiang 1.
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Qi Xin 1.
Nanozyme Laboratory in Zhongyuan, Henan Academy of Innovations in Medical Science, Zhengzhou, China
Xiyun Yan & Bing Jiang 1.
CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
Xiyun Yan
Authors
- Yale Yue
- Qi Xin
- Yuanyuan Zhu
- Dandan Zhu
- Baohua Zhang
- Xiyun Yan
- Bing Jiang
Contributions
Y.Y. and Q.X. contributed equally to this work. X.Y. and B.J. conceptualized and designed the project. Y.Y., Q.X., and Y.Z. performed the research. All authors analyzed and interpreted the data. B.J. and X.Y. supervised the project. Y.Y. and B.J. wrote the paper.
Corresponding authors
Correspondence to Xiyun Yan or Bing Jiang.
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Nature Communications thanks Songping Zhang and Stéphane Paul for their contribution to the peer review of this work. A peer review file is available.
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Cite this article
Yue, Y., Xin, Q., Zhu, Y. et al. Probiotic-based oral vaccine mucosal delivery system enabling genetically encoded dual-antigen arrays. Nat Commun (2025). https://doi.org/10.1038/s41467-025-66622-x
Received: 07 May 2025
Accepted: 11 November 2025
Published: 22 November 2025
DOI: https://doi.org/10.1038/s41467-025-66622-x