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

作者：Yinbo Jiang, Nanxuan Huang, Lixia Huang, Xinyuan Li, X. Zhang, Gang Zheng, Tayier Tuerhong, Han Liu, Jiaxi Lai, Chunmei Liang, Xiaohui Zhang, Liuyuan Wang, Rongyi Chen, Cailing Ao, Bin Yang, Wujian Ke · 发表于：npj Vaccines · 年份：2025 · DOI：10.1038/s41541-025-01330-7 · 被引用次数：1 · 研究领域：Syphilis Diagnosis and Treatment、Reproductive tract infections research、Reproductive System and Pregnancy

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 T1 ) delivered via two platforms: lipid nanoparticle–encapsulated nucleoside-modified mRNA (LNP-mRNA) and Pyrococcus furiosus thioredoxin ( Pf 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 T1 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 Pf Trx-Tp0136 T1 , while LNP-mRNA-Tp0136 T1 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.