Zeng Lingyuan, Zuo You, Tang Minghui, Lei Chengrui, Li Huoming, Ma Xiuling, Ji Jiahong, Li Hao
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.
iScience. 2024 Dec 20;28(1):111568. doi: 10.1016/j.isci.2024.111568. eCollection 2025 Jan 17.
The importance of humoral immunity in combating TB has gained extensive recognition. In this study, a subunit vaccine named Ag85A-LpqH (AL) was prepared by fusing the antigen Ag85A proved to induce robust T cell immune responses, and LpqH was shown to produce protective antibodies. The prevention and BCG prime-boost mouse models were established to test the vaccine efficacy. The results indicate that Ag85A-LpqH can induce substantial protection by reducing bacterial loads and pathological lesions. This vaccine can induce robust antibody responses, as well as T cell immune responses especially strong CD8 T cell responses. Moreover, the serum from AL-immunized mice can reduce the bacterial load and lung pathology in mice. B cell receptor (BCR) sequencing revealed a notable rise in BCR diversity among mice immunized with AL. These results indicate that Ag85A-LpqH can be a promising vaccine candidate for tuberculosis prevention and control.
体液免疫在抗击结核病中的重要性已得到广泛认可。在本研究中，通过融合被证明能诱导强烈T细胞免疫反应的抗原Ag85A和被证明能产生保护性抗体的LpqH，制备了一种名为Ag85A-LpqH（AL）的亚单位疫苗。建立了预防和卡介苗初免-加强免疫小鼠模型以测试疫苗效力。结果表明，Ag85A-LpqH可通过降低细菌载量和病理损伤诱导显著的保护作用。该疫苗可诱导强烈的抗体反应以及T细胞免疫反应，尤其是强烈的CD8 T细胞反应。此外，来自AL免疫小鼠的血清可降低小鼠的细菌载量和肺部病理损伤。B细胞受体（BCR）测序显示，用AL免疫的小鼠中BCR多样性显著增加。这些结果表明，Ag85A-LpqH可能是一种有前景的结核病预防和控制疫苗候选物。
