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表达尼帕病毒F和G糖蛋白的重组水疱性口炎病毒的研制及免疫原性评价

Development and Immunogenic Evaluation of a Recombinant Vesicular Stomatitis Virus Expressing Nipah Virus F and G Glycoproteins.

作者信息

Guo Huijuan, Liu Renqiang, Pan Dan, Dang Yijing, Meng Shuhuai, Shan Dan, Wang Xijun, Ge Jinying, Bu Zhigao, Wen Zhiyuan

机构信息

State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China.

Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225000, China.

出版信息

Viruses. 2025 Jul 31;17(8):1070. doi: 10.3390/v17081070.

DOI:10.3390/v17081070
PMID:40872782
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12390688/
Abstract

Nipah virus (NiV) is a highly pathogenic bat-borne zoonotic pathogen that poses a significant threat to human and animal health, with fatality rates exceeding 70% in some outbreaks. Despite its significant public health impact, there are currently no licensed vaccines or specific therapeutics available. Various virological tools-such as reverse genetics systems, replicon particles, VSV-based pseudoviruses, and recombinant Cedar virus chimeras-have been widely used to study the molecular mechanisms of NiV and to support vaccine development. Building upon these platforms, we developed a replication-competent recombinant vesicular stomatitis virus (rVSVΔG-eGFP-NiV F/G) expressing NiV attachment (G) and fusion (F) glycoproteins. This recombinant virus serves as a valuable tool for investigating NiV entry mechanisms, cellular tropism, and immunogenicity. The virus was generated by replacing the VSV G protein with NiV F/G through reverse genetics, and protein incorporation was confirmed via immunofluorescence and electron microscopy. In vitro, the virus exhibited robust replication, characteristic cell tropism, and high viral titers in multiple cell lines. Neutralization assays showed that monoclonal antibodies HENV-26 and HENV-32 effectively neutralized the recombinant virus. Furthermore, immunization of golden hamsters with inactivated rVSVΔG-eGFP-NiV F/G induced potent neutralizing antibody responses, demonstrating its robust immunogenicity. These findings highlight rVSVΔG-eGFP-NiV F/G as an effective platform for NiV research and vaccine development.

摘要

尼帕病毒(NiV)是一种高致病性的蝙蝠源性人畜共患病原体,对人类和动物健康构成重大威胁,在某些疫情中病死率超过70%。尽管其对公共卫生有重大影响,但目前尚无获批的疫苗或特效治疗药物。各种病毒学工具,如反向遗传学系统、复制子颗粒、基于水疱性口炎病毒(VSV)的假病毒和重组雪松病毒嵌合体,已被广泛用于研究尼帕病毒的分子机制并支持疫苗开发。在这些平台的基础上,我们构建了一种具有复制能力的重组水疱性口炎病毒(rVSVΔG-eGFP-NiV F/G),其表达尼帕病毒的附着(G)糖蛋白和融合(F)糖蛋白。这种重组病毒是研究尼帕病毒进入机制、细胞嗜性和免疫原性的宝贵工具。该病毒通过反向遗传学用尼帕病毒F/G取代VSV G蛋白而产生,并通过免疫荧光和电子显微镜确认了蛋白的掺入。在体外,该病毒在多种细胞系中表现出强劲的复制能力、典型的细胞嗜性和高病毒滴度。中和试验表明,单克隆抗体HENV-26和HENV-32能有效中和该重组病毒。此外,用灭活的rVSVΔG-eGFP-NiV F/G免疫金黄仓鼠可诱导产生强效的中和抗体反应,证明其具有强大的免疫原性。这些发现突出了rVSVΔG-eGFP-NiV F/G作为尼帕病毒研究和疫苗开发的有效平台的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/f59b261615f5/viruses-17-01070-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/871a3b6e6a57/viruses-17-01070-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/dea237c2e040/viruses-17-01070-g0A2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/2687a82df92a/viruses-17-01070-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/9f1250d01859/viruses-17-01070-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/e871eef242dc/viruses-17-01070-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/4906de6af5f1/viruses-17-01070-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/f59b261615f5/viruses-17-01070-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/871a3b6e6a57/viruses-17-01070-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/dea237c2e040/viruses-17-01070-g0A2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/2687a82df92a/viruses-17-01070-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/9f1250d01859/viruses-17-01070-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/e871eef242dc/viruses-17-01070-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/4906de6af5f1/viruses-17-01070-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e5/12390688/f59b261615f5/viruses-17-01070-g005.jpg

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Emerg Microbes Infect. 2025 Dec;14(1):2449083. doi: 10.1080/22221751.2024.2449083. Epub 2025 Jan 12.
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Nipah Virus Outbreaks in Kerala: An Impending Doom?喀拉拉邦的尼帕病毒疫情:一场迫在眉睫的灾难?
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Optimization of Bangladesh and Malaysian genotype recombinant reporter Nipah viruses for in vitro antiviral screening and in vivo disease modeling.
孟加拉国和马来西亚基因型重组报告性尼帕病毒的体外抗病毒筛选和体内疾病建模优化。
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Establishment of replication-competent vesicular stomatitis virus recapitulating SADS-CoV entry.建立复制型水疱性口炎病毒重现 SADS-CoV 进入的过程。
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Establishment and application of a surrogate model for human Ebola virus disease in BSL-2 laboratory.建立和应用在二级生物安全实验室中人类埃博拉病毒病的替代模型。
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