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<p>Syphilis, caused by <i>Treponema pallidum</i>, remains a major global health burden. Given the key role of T cell–mediated immunity in <i>T. pallidum</i> 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 <i>Pyrococcus furiosus</i> thioredoxin (<i>Pf</i>Trx). 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 <i>T. pallidum</i>, complete ulcer prevention was achieved with the <i>Pf</i>Trx-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.</p>

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Protective immunity induced by Tp0136 epitope vaccines with mRNA LNP or protein delivery

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月12日

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  • Yinbo Jiang,
  • Nanxuan Huang,
  • Lixia Huang,
  • Xinyuan Li,
  • Xiangcai Zhang,
  • Gang Zheng,
  • Tayier Tuerhong,
  • Han Liu,
  • Jiaxi Lai,
  • Chunmei Liang,
  • Xiaohui Zhang,
  • Liuyuan Wang,
  • Rongyi Chen,
  • Cailing Ao,
  • Bin Yang,
  • Wujian Ke

摘要

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 (Tp0136T1) 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-Tp0136T1 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-Tp0136T1, while LNP-mRNA-Tp0136T1 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.