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针对猴痘的多基因缺失痘苗病毒天坛株

Multiple gene-deletion vaccinia virus Tiantan strain against mpox.

作者信息

Zhu Yilong, Li Dapeng, Zhao Renshuang, Chen Minghua, Li Yue, Yang Xia, Mao Hongyue, Li Xiao, Li Yiquan, Shang Chao, Xia Xianzhu

机构信息

Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, People's Republic of China.

Key Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, 130117, People's Republic of China.

出版信息

Virol J. 2025 Jan 25;22(1):17. doi: 10.1186/s12985-025-02629-6.

DOI:10.1186/s12985-025-02629-6
PMID:39863910
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11762464/
Abstract

Monkeypox virus (MPXV) is an important zoonotic pathogenic virus, which poses serious threats to public health. MPXV infection can be prevented by immunization against the variola virus. Because of the safety risks and side effects of vaccination with live vaccinia virus (VACV) strain Tian Tan (VTT), we constructed two gene-deleted VTT recombinants (TTVAC7 and TTVC5). The immunogenicity and protective effects of the gene-deleted VTT vaccine were assessed using BALB/C mice challenged with VTT and New Zealand rabbits challenged with MPXV. The results demonstrated strong humoral and cellular immune responses. The VTT-specific and neutralizing antibody titers, specific T cell levels, and degree of dendritic cell maturation of the mice, in addition to the MPXV neutralizing antibody titers and IFN-γ, IL-6, and TNF-α levels of the rabbits were markedly higher in the groups immunized with TTVAC7 and TTVC5 than the control groups (p < 0.05). Moreover, immunization with TTVAC7 and TTVC5 reduced morbidities caused by VACV and MPXV infection. The weight change, lung histological score, and residual virus of the mouse model (p < 0.05). Similarly, the temperature change, pock number, lung histological score, and residual virus of the rabbit model were significantly reduced in the groups immunized with TTVAC7 and TTVC5 (p < 0.05). Collectively, these results demonstrate that TTVAC7 and TTVC5 may be used as potential live attenuated vaccines against MPXV infection.

摘要

猴痘病毒(MPXV)是一种重要的人畜共患病致病病毒,对公众健康构成严重威胁。接种天花病毒疫苗可预防MPXV感染。由于使用天坛株痘苗病毒(VACV)(VTT)进行疫苗接种存在安全风险和副作用,我们构建了两种基因缺失的VTT重组体(TTVAC7和TTVC5)。使用感染VTT的BALB/C小鼠和感染MPXV的新西兰兔评估基因缺失的VTT疫苗的免疫原性和保护效果。结果显示出强烈的体液免疫和细胞免疫反应。在接种TTVAC7和TTVC5的组中,小鼠的VTT特异性中和抗体滴度、特异性T细胞水平和树突状细胞成熟度,以及兔子的MPXV中和抗体滴度和IFN-γ、IL-6和TNF-α水平均明显高于对照组(p < 0.05)。此外,接种TTVAC7和TTVC5降低了由VACV和MPXV感染引起的发病率。小鼠模型的体重变化、肺组织学评分和残余病毒量(p < 0.05)。同样,在接种TTVAC7和TTVC5的组中,兔子模型的体温变化、痘疹数量、肺组织学评分和残余病毒量均显著降低(p < 0.05)。总体而言,这些结果表明TTVAC7和TTVC5可作为预防MPXV感染的潜在减毒活疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e56/11762464/7c1e5950d175/12985_2025_2629_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e56/11762464/fcf600d68b46/12985_2025_2629_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e56/11762464/16d53a288c9a/12985_2025_2629_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e56/11762464/b0b590c1cd3d/12985_2025_2629_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e56/11762464/8b72c4295623/12985_2025_2629_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e56/11762464/e9836859a5d6/12985_2025_2629_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e56/11762464/7c1e5950d175/12985_2025_2629_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e56/11762464/fcf600d68b46/12985_2025_2629_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e56/11762464/16d53a288c9a/12985_2025_2629_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e56/11762464/b0b590c1cd3d/12985_2025_2629_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e56/11762464/8b72c4295623/12985_2025_2629_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e56/11762464/e9836859a5d6/12985_2025_2629_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e56/11762464/7c1e5950d175/12985_2025_2629_Fig6_HTML.jpg

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本文引用的文献

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Re-emergence of Mpox associated with a distinct MPXV clade: implications for public health and stigma mitigation.与一个独特的猴痘病毒分支相关的猴痘再度出现:对公共卫生和减轻污名化的影响。
Infect Dis (Lond). 2024 Oct;56(10):928-929. doi: 10.1080/23744235.2024.2388835. Epub 2024 Aug 6.
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The 2023 - 2024 multi-source mpox outbreaks of Clade I MPXV in sub-Saharan Africa: Alarm bell for Africa and the World.2023 - 2024年撒哈拉以南非洲地区I类猴痘病毒多源猴痘疫情:给非洲和世界敲响的警钟。
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Polygenic TB control and the sequence of innate/adaptive immune responses to infection: MHC-II alleles determine the size of the S100A8/9-producing neutrophil population.
多基因结核病控制与感染后固有/适应性免疫反应的顺序:MHC-II 等位基因决定 S100A8/9 产生中性粒细胞群体的大小。
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Human MHC Class II and Invariant Chain Knock-in Mice Mimic Rheumatoid Arthritis with Allele Restriction in Immune Response and Arthritis Association.人类 MHC II 类和不变链敲入小鼠模拟类风湿关节炎,具有免疫反应和关节炎相关性的等位基因限制。
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Role of inflammatory signaling pathways involving the CD40-CD40L-TRAF cascade in diabetes and hypertension-insights from animal and human studies.涉及 CD40-CD40L-TRAF 级联的炎症信号通路在糖尿病和高血压中的作用:来自动物和人类研究的见解。
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