State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, China.
Virulence. 2023 Dec;14(1):2280377. doi: 10.1080/21505594.2023.2280377. Epub 2023 Nov 19.
Brucellosis, caused by , is a severe zoonosis, and the current live attenuated vaccine cannot be used in humans due to major safety risks. Although polysaccharide antigens can be used to prepare the vaccine, their lower immunogenicity limits them from producing efficient and broad protection. In this study, we produced a high-performance bioconjugate nanovaccine against different species of by introducing a self-assembly nanoparticle platform and an O-linked glycosylation system into serotype O:9, which has an -polysaccharide composed of the same unit as . After successfully preparing the vaccine and confirming its stability, we subsequently demonstrated the safety of the vaccine in mice by high-dose immunization. Then, by a series of mouse experiments, we found that the nanovaccine greatly promoted antibody responses. In particular, the increase of IgG2a was more obvious than that of IgG1. Most importantly, this nanovaccine could provide cross-protection against , , and strains by lethal dose challenged models, and could improve the clearance of , the most common pathogenic species in human brucellosis, by non-lethal dose infection. Overall, for the first time, we biocoupled polysaccharide antigens with nano carriers to prepare a vaccine, which showed pronounced and extensive protective effects in mice. Thus, we provided a potential candidate vaccine and a new direction for vaccine design.
布鲁氏菌病由布鲁氏菌引起，是一种严重的人畜共患病，由于存在重大安全风险，目前的活减毒疫苗不能在人类中使用。尽管多糖抗原可用于制备疫苗，但由于其免疫原性较低，限制了它们产生高效和广泛保护的能力。在这项研究中，我们通过将自组装纳米颗粒平台和 O 连接糖基化系统引入到血清型 O:9 中，生产了一种针对不同种布鲁氏菌的高性能生物偶联纳米疫苗，该血清型 O:9 具有与布鲁氏菌相同单元组成的 O-多糖。成功制备疫苗并确认其稳定性后，我们随后通过高剂量免疫在小鼠中证明了疫苗的安全性。然后，通过一系列小鼠实验，我们发现纳米疫苗大大促进了抗体反应。特别是 IgG2a 的增加比 IgG1 更为明显。最重要的是，这种纳米疫苗可以通过致死剂量挑战模型对、和菌株提供交叉保护，并且可以通过非致死剂量感染来提高最常见的人布鲁氏菌病致病性物种的清除率。总的来说，这是首次将多糖抗原与纳米载体生物偶联来制备布鲁氏菌疫苗，在小鼠中表现出明显和广泛的保护作用。因此，我们为布鲁氏菌疫苗设计提供了一个有潜力的候选疫苗和新方向。
