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针对 A/Shanghai/1/2013(H7N9)血凝素的交叉反应性鼠单克隆抗体可在小鼠模型中预防新型 H7 病毒分离株。

Cross-reactive mouse monoclonal antibodies raised against the hemagglutinin of A/Shanghai/1/2013 (H7N9) protect against novel H7 virus isolates in the mouse model.

机构信息

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.

出版信息

Emerg Microbes Infect. 2018 Jun 20;7(1):110. doi: 10.1038/s41426-018-0115-0.

DOI:10.1038/s41426-018-0115-0
PMID:29925896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6010460/
Abstract

Influenza viruses remain a major global public health risk. In addition to seasonal influenza viruses, epizootic influenza A H7 subtype viruses of both the Asian and North American lineage are of concern due to their pandemic potential. In China, the simultaneous occurrence of H7N9 zoonotic episodes and seasonal influenza virus epidemics could potentially lead to novel reassortant viruses with the ability to efficiently spread among humans. Recently, the H7N9 virus has evolved into two new lineages, the Pearl River Delta and the Yangtze River Delta clade. This development has also resulted in viruses with a polybasic cleavage site in the hemagglutinin that are highly pathogenic in avian species and have caused human infections. In addition, an outbreak of a highly pathogenic H7N8 strain was reported in the US state of Indiana in 2016. Furthermore, an H7N2 feline virus strain caused an outbreak in cats in an animal shelter in New York City in 2016, resulting in one human zoonotic event. In this study, mouse monoclonal antibodies previously raised against the hemagglutinin of the A/Shanghai/1/2013 (H7N9) virus were tested for their (cross-) reactivity to these novel H7 viruses. Moreover, the functionality of these antibodies was assessed in vitro in hemagglutination inhibition and microneutralization assays. The therapeutic and prophylactic efficacy of the broadly reactive antibodies against novel H7 viruses was determined in vivo in mouse passive transfer-viral challenge experiments. Our results provide data about the conservation of critical H7 epitopes and could inform the selection of pre-pandemic H7 vaccine strains.

摘要

流感病毒仍然是一个主要的全球公共卫生风险。除了季节性流感病毒外,亚洲和北美的甲型 H7 亚型流行流感病毒也因其大流行潜力而受到关注。在中国,H7N9 人畜共患病的同时发生和季节性流感病毒的流行可能导致具有在人群中高效传播能力的新型重组病毒。最近,H7N9 病毒已经进化成两个新的谱系,即珠江三角洲和长江三角洲分支。这种发展还导致了血凝素中具有多碱性裂解位点的病毒,这些病毒在禽类中具有高致病性,并导致人类感染。此外,2016 年美国印第安纳州报告了一起高致病性 H7N8 株的爆发。此外,2016 年,纽约市一家动物收容所的一只 H7N2 猫流感病毒株导致猫群爆发,导致一起人间人畜共患病事件。在这项研究中,先前针对 A/上海/2013(H7N9)病毒血凝素产生的鼠单克隆抗体被测试了其对这些新型 H7 病毒的(交叉)反应性。此外,这些抗体的功能在体外的血凝抑制和微量中和试验中进行了评估。在小鼠被动转移-病毒挑战实验中,体内实验确定了这些广泛反应性抗体对新型 H7 病毒的治疗和预防效果。我们的结果提供了关于关键 H7 表位保守性的信息,并为选择大流行前的 H7 疫苗株提供了信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaca/6010460/cd77b5d500ab/41426_2018_115_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaca/6010460/68a1e68bdbcf/41426_2018_115_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaca/6010460/79ce0dbca5ff/41426_2018_115_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaca/6010460/231bf0a56f7a/41426_2018_115_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaca/6010460/59fd7f569332/41426_2018_115_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaca/6010460/27a6d076c08e/41426_2018_115_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaca/6010460/cd77b5d500ab/41426_2018_115_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaca/6010460/68a1e68bdbcf/41426_2018_115_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaca/6010460/79ce0dbca5ff/41426_2018_115_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaca/6010460/231bf0a56f7a/41426_2018_115_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaca/6010460/59fd7f569332/41426_2018_115_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaca/6010460/27a6d076c08e/41426_2018_115_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaca/6010460/cd77b5d500ab/41426_2018_115_Fig6_HTML.jpg

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