Li Shulei, Huang Jing, Wang Kangfeng, Liu Yan, Guo Yan, Li Xiang, Wu Jun, Sun Peng, Wang Yufei, Zhu Li, Wang Hengliang
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, China.
The Third Medical Center, PLA General Hospital, Beijing, China.
Front Bioeng Biotechnol. 2023 Feb 23;11:1121074. doi: 10.3389/fbioe.2023.1121074. eCollection 2023.
Brucellosis, mainly caused by is a widespread zoonotic disease worldwide, with no available effective vaccine for human use. Recently, bioconjugate vaccines against have been prepared in O:9 (YeO9), whose O-antigen structure is similar to that of . However, the pathogenicity of YeO9 still hinders the large-scale production of these bioconjugate vaccines. Here, an attractive system for the preparation of bioconjugate vaccines against was established in engineered . Briefly, the OPS gene cluster of YeO9 was modularized into five individual fragments and reassembled using synthetic biological methods through standardized interfaces, then introduced into . After confirming the synthesis of targeted antigenic polysaccharides, the exogenous protein glycosylation system (PglL system) was used to prepare the bioconjugate vaccines. A series of experiments were conducted to demonstrate that the bioconjugate vaccine could effectively evoke humoral immune responses and induce the production of specific antibodies against A19 lipopolysaccharide. Furthermore, the bioconjugate vaccines provide protective roles in both lethal and non-lethal challenge of A19 strain. Using the engineered as a safer chassis to prepare bioconjugate vaccines against paves the way for future industrial applications.
布鲁氏菌病主要由[具体病原体]引起,是一种在全球广泛传播的人畜共患病,目前尚无有效的人用疫苗。最近,已在[具体菌株]O:9(YeO9)中制备了针对[具体病原体]的生物共轭疫苗,其O抗原结构与[具体病原体]相似。然而,YeO9的致病性仍然阻碍了这些生物共轭疫苗的大规模生产。在此,利用工程化的[具体菌株]建立了一种制备针对[具体病原体]的生物共轭疫苗的有效系统。简要地说,将YeO9的OPS基因簇模块化分成五个独立片段,并通过标准化接口利用合成生物学方法进行重新组装,然后导入[具体菌株]。在确认合成了靶向抗原多糖后,使用外源蛋白糖基化系统(PglL系统)制备生物共轭疫苗。进行了一系列实验以证明该生物共轭疫苗能够有效激发体液免疫反应并诱导产生针对[具体病原体]A19脂多糖的特异性抗体。此外,该生物共轭疫苗在[具体病原体]A19菌株的致死和非致死攻击中均发挥保护作用。利用工程化的[具体菌株]作为更安全的底盘来制备针对[具体病原体]的生物共轭疫苗,为未来的工业应用铺平了道路。