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一种新型病毒样颗粒疫苗可诱导仔猪对三角洲冠状病毒产生广泛的免疫保护。

A novel virus-like particles vaccine induces broad immune protective against deltacoronavirus in piglets.

作者信息

Zhang Baotai, Li Siyuan, Zhou Jinzhu, Wang Wei, Xiao Li, Yuan Xuesong, Yi Xin, Fan Liyuan, Fan Baochao, Zhu Xing, Li Jizong, Li Bin

机构信息

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing, 210014, China; College of Animal Science, Guizhou University, Guiyang, 550025, China.

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing, 210014, China.

出版信息

Virology. 2024 Sep;597:110150. doi: 10.1016/j.virol.2024.110150. Epub 2024 Jun 21.

Abstract

Coronaviruses (CoVs) comprise a group of important human and animal pathogens that threaten public health because of their interspecies transmission potential to humans. However, virus-like particles (VLPs) constitute versatile tools in CoVs vaccine development due to their favorable immunological characteristics. Here, we engineered the VLPs composed of the spike (S), membrane (M), and envelope (E) structural proteins of the Porcine deltacoronavirus (PDCoV) and examined their immune responses in mice. Neutralization assays and flow Cytometry demonstrated that PDCoV VLPs induced highly robust neutralizing antibodies (NAbs) and elicited cellular immunity. To assess the protective efficacy of VLPs in newborn piglets, pregnant sows received vaccinations with either a PDCoV-inactivated vaccine or VLPs at 40 and 20 days before delivery. Five days post-farrowing, piglets were orally challenged with the PDCoV strain. Severe diarrhea, high viral RNA copies, and substantial intestinal villus atrophy were detected in piglets born to unimmunized sows. However, piglets from sows immunized with VLPs exhibited high NAbs titers and markedly reduced microscopic damage to the intestinal tissues, with no piglet showing diarrhea. Hence, the results indicate that the VLPs are a potential clinical candidate for PDCoV vaccination, while the strategy may serve as a platform for developing other coronavirus vaccines.

摘要

冠状病毒(CoVs)是一类重要的人类和动物病原体,因其具有跨物种传播给人类的潜力而威胁公共卫生。然而,病毒样颗粒(VLPs)由于其良好的免疫学特性,在冠状病毒疫苗开发中构成了多功能工具。在此,我们构建了由猪德尔塔冠状病毒(PDCoV)的刺突(S)、膜(M)和包膜(E)结构蛋白组成的病毒样颗粒,并检测了它们在小鼠体内的免疫反应。中和试验和流式细胞术表明,PDCoV病毒样颗粒诱导产生了高度强大的中和抗体(NAbs)并引发了细胞免疫。为了评估病毒样颗粒对新生仔猪的保护效果,在分娩前40天和20天,给怀孕母猪接种PDCoV灭活疫苗或病毒样颗粒。分娩后五天,用PDCoV毒株对仔猪进行口服攻毒。在未免疫母猪所产仔猪中检测到严重腹泻、高病毒RNA拷贝数和明显的肠绒毛萎缩。然而,用病毒样颗粒免疫的母猪所产仔猪表现出高NAb滴度,对肠道组织的微观损伤明显减少,没有仔猪出现腹泻。因此,结果表明病毒样颗粒是PDCoV疫苗接种的潜在临床候选物,而该策略可作为开发其他冠状病毒疫苗的平台。

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