Protective immunity induced by Tp0136 epitope vaccines with mRNA LNP or protein delivery
Syphilis, caused by Treponema pallidum, remains a major global health burden. Given the key role of T cell-mediated immunity in T. pallidum clearance, this study evaluates a Tp0136-derived T-cell epitope (Tp0136<sup>T1</sup>) delivered via two platforms: lipid nanoparticle-encapsulated nucleoside-modified mRNA (LNP-mRNA) and Pyrococcus furiosus thioredoxin (PfTrx). In BALB/c mice, both platforms elicited robust Th1-type responses, with increased IL-2 and IFN-γ secretion and activation of Th1 CD4⁺ T cell. Only LNP-mRNA-Tp0136<sup>T1</sup> induced strong CD8⁺ cytotoxic responses, marked by elevated perforin⁺ and granzyme B⁺ expression. In New Zealand White rabbits challenged intradermally with T. pallidum, complete ulcer prevention was achieved with the PfTrx-Tp0136<sup>T1</sup>, while LNP-mRNA-Tp0136<sup>T1</sup> significantly reduced ulceration. Both vaccines suppressed RPR titers and lowered treponemal load. These findings demonstrate that epitope-specific T cell-based vaccines elicit potent cellular immunity, control treponemes, prevent ulcers, and may reduce secondary sexually transmitted infections by preserving mucosal integrity.
Authors
- J. C. K. Lai (ORCID: https://orcid.org/0000-0001-5841-1134)
- Liuyuan Wang (ORCID: https://orcid.org/0000-0001-5390-7608)
- Cailing Ao
- Chunmei Liang (ORCID: https://orcid.org/0000-0003-1639-7543)
- Lixia Huang (ORCID: https://orcid.org/0009-0007-9416-8507)
- Yinbo Jiang
- Rongyi Chen (ORCID: https://orcid.org/0009-0000-2454-9450)
- Han Liu (ORCID: https://orcid.org/0000-0001-7753-9205)
- Xiaohui Zhang (ORCID: https://orcid.org/0000-0003-0245-6792)
- Gang Zheng (ORCID: https://orcid.org/0000-0003-4326-7226)
- Bin Yang (ORCID: https://orcid.org/0000-0002-7883-0739)
- Wujian Ke (ORCID: https://orcid.org/0000-0003-4800-4302)
- Nanxuan Huang (ORCID: https://orcid.org/0009-0009-6729-2507)
- X. Zhang (ORCID: https://orcid.org/0009-0001-1638-4120)
- Tayier Tuerhong
Institutions
- Chinese Center For Disease Control and Prevention (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Guangzhou Center for Disease Control and Prevention (CN)
- Chinese Academy of Medical Sciences Dermatology Hospital (CN)
- Zhujiang Hospital (CN)
- Nanjing Municipal Center for Disease Control And Prevention (CN)
- Kashi University (CN)
- Southern Medical University (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- npj Vaccines
- Published
- 2025-12-12
- DOI
- https://doi.org/10.1038/s41541-025-01330-7
- Primary Topic
- Syphilis Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Connecticut
- National Natural Science Foundation of China
- Natural Science Foundation of Guangdong Province
- Southern Medical University
- HORIZON EUROPE Framework Programme