Ding Yanbin, Li Yuanyuan, Wu Zhuhua, Zhou Yu, Guo Yan, Tian Siyu, Yu Rui, Deng Chunping, Wei Rui, Chen Hang, Li Yan, Zhang Xiaokang, Yu Wenjia, Jing Cai, Liu Shuyun, Qin Lili, Lyu Meng, Zou Yongjuan, Yao Yuanfeng, Tan Lu, Wu Shifen, Liu Weilong, Chen Xunxun, Jin Jing
Patronus Biotech Co. Ltd., Guangzhou, China.
Institute for Tuberculosis Research, Center for Tuberculosis Control of Guangdong Province, Guangzhou, Guangdong, China.
NPJ Vaccines. 2025 Jul 29;10(1):173. doi: 10.1038/s41541-025-01216-8.
Tuberculosis remains a major global health threat, as Bacillus Calmette-Guérin (BCG), the only licensed vaccine, provides limited protection, particularly in adolescents and adults. To address this limitation, a more effective tuberculosis vaccine was developed using the SpyTag/SpyCatcher system to display five clinically validated Mycobacterium tuberculosis antigens (Ag85A, ESAT-6, CFP10, Rv2660c, and TB10.4) on self-assembling mi3 nanoparticles. These nanoparticle-displayed antigens, formulated as 85A-NP, EC-NP, and RT-NP and combined with a custom AS01E-biosimilar adjuvant, elicited stronger Th1-biased immune responses in C57BL/6 mice than the corresponding recombinant proteins, as evidenced by increased frequencies of polyfunctional CD4⁺ T cells producing IFN-γ, IL-2, and TNF-α. In a murine aerosol challenge model, the mixed nanoparticles formulation (85A-NP:EC-NP:RT-NP) conferred superior pulmonary protection compared to single-antigen nanoparticles, recombinant protein mixtures, an in-house M72-like vaccine and BCG. This modular platform enables efficient multistage antigen incorporation and holds promise for next-generation tuberculosis vaccine development.
结核病仍然是全球主要的健康威胁，因为唯一获得许可的疫苗卡介苗（BCG）提供的保护有限，尤其是在青少年和成年人中。为了解决这一局限性，利用SpyTag/SpyCatcher系统开发了一种更有效的结核病疫苗，以便在自组装的mi3纳米颗粒上展示五种经过临床验证的结核分枝杆菌抗原（Ag85A、ESAT-6、CFP10、Rv2660c和TB10.4）。这些纳米颗粒展示的抗原，配制成85A-NP、EC-NP和RT-NP，并与定制的AS01E生物类似佐剂结合，在C57BL/6小鼠中引发了比相应重组蛋白更强的Th1偏向性免疫反应，这通过产生IFN-γ、IL-2和TNF-α的多功能CD4⁺ T细胞频率增加得到证明。在小鼠气溶胶攻击模型中，与单抗原纳米颗粒、重组蛋白混合物、内部M72样疫苗和卡介苗相比，混合纳米颗粒制剂（85A-NP:EC-NP:RT-NP）提供了更好的肺部保护。这个模块化平台能够高效地进行多阶段抗原整合，并为下一代结核病疫苗的开发带来希望。
