Guo Fangzheng, Dong Sihang, Song Yamin, Xiesihan Ge, Jiang Hairui, Qian Zhongqing, Wang Xiaojing, Wang Hongtao, Xu Tao
Anhui Province Key Laboratory of Immunology in Chronic Diseases, Laboratory Medicine Experimental Center, Laboratory Medicine College, Bengbu Medical University, Bengbu 233000, China.
Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
Int Immunopharmacol. 2025 Aug 28;161:115019. doi: 10.1016/j.intimp.2025.115019. Epub 2025 Jun 12.
Although Bacillus Calmette-Guérin (BCG) continues to play a role in alleviating tuberculosis as a global public health crisis, its potential to cause disseminated disease in immunocompromised individuals further limits its widespread use. However, traditional subunit vaccines face the challenge of weak immunogenicity. In this study, we employed the SpyCatcher/SpyTag system and a ferritin (Fer) nanoparticle (NP) to construct an NP-based vaccine targeting the non-region of difference antigen TB10.4. The construct comprises two components: a SpyCatcher003-Fer vector and SpyTag003-TB10.4 antigen, expressed in prokaryotic and eukaryotic systems, respectively. These components were self-assembled into the tuberculosis nanovaccine candidate, SpyCatcher-Fer-TB10.4 (SFT), in vitro. Compared with the monomeric TB10.4, subcutaneous immunization with SFT-without an adjuvant-markedly enhanced cell proliferation, promoted T lymphocyte activation, and stimulated multiple TB-related cytokines, with responses comparable to or exceeding those induced by BCG. These findings suggest that SFT is superior to conventional recombinant proteins and holds promise for eliciting immunoprotective effects similar to those of BCG in the future.
尽管卡介苗（BCG）在缓解作为全球公共卫生危机的结核病方面仍发挥着作用，但其在免疫功能低下个体中引发播散性疾病的可能性进一步限制了其广泛应用。然而，传统亚单位疫苗面临免疫原性弱的挑战。在本研究中，我们利用SpyCatcher/SpyTag系统和铁蛋白（Fer）纳米颗粒（NP）构建了一种靶向差异抗原TB10.4非区域的基于NP的疫苗。该构建体包含两个组分：分别在原核和真核系统中表达的SpyCatcher003-Fer载体和SpyTag003-TB10.4抗原。这些组分在体外自组装成结核病纳米疫苗候选物SpyCatcher-Fer-TB10.4（SFT）。与单体TB10.4相比，无佐剂的SFT皮下免疫显著增强细胞增殖，促进T淋巴细胞活化，并刺激多种结核相关细胞因子，其反应与卡介苗诱导的反应相当或超过卡介苗诱导的反应。这些发现表明，SFT优于传统重组蛋白，有望在未来引发与卡介苗相似的免疫保护作用。
