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Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease.
Science Immunology ( IF 17.6 ) Pub Date : 2020-07-03 , DOI: 10.1126/sciimmunol.aba4902
Matthew R Vogt 1 , Jianing Fu 2 , Nurgun Kose 3 , Lauren E Williamson 4 , Robin Bombardi 3 , Ian Setliff 5 , Ivelin S Georgiev 3, 4 , Thomas Klose 2 , Michael G Rossmann 2 , Yury A Bochkov 6 , James E Gern 6, 7 , Richard J Kuhn 2 , James E Crowe 1, 3, 4, 5
Affiliation  

Enterovirus D68 (EV-D68) causes outbreaks of respiratory illness, and there is increasing evidence that it causes outbreaks of acute flaccid myelitis (AFM). There are no licensed therapies to prevent or treat EV-D68 infection or AFM disease. We isolated a panel of EV-D68–reactive human monoclonal antibodies that recognize diverse antigenic variants from participants with prior infection. One potently neutralizing cross-reactive antibody, EV68-228, protected mice from respiratory and neurologic disease when given either before or after infection. Cryo–electron microscopy studies revealed that EV68-228 and another potently neutralizing antibody (EV68-159) bound around the fivefold or threefold axes of symmetry on virion particles, respectively. The structures suggest diverse mechanisms of action by these antibodies. The high potency and effectiveness observed in vivo suggest that antibodies are a mechanistic correlate of protection against AFM disease and are candidates for clinical use in humans with EV-D68 infection.



中文翻译:

人类抗体中和肠道病毒 D68 并防止感染和麻痹性疾病。

肠道病毒 D68 (EV-D68) 会导致呼吸道疾病的爆发,越来越多的证据表明它会导致急性弛缓性脊髓炎 (AFM) 的爆发。没有获得许可的疗法来预防或治疗 EV-D68 感染或 AFM 疾病。我们分离了一组 EV-D68 反应性人单克隆抗体,这些抗体可识别来自先前感染参与者的多种抗原变体。一种有效的中和交叉反应抗体 EV68-228 在感染前或感染后给予小鼠以保护小鼠免受呼吸系统和神经系统疾病的侵害。冷冻电子显微镜研究表明,EV68-228 和另一种强效中和抗体 (EV68-159) 分别结合在病毒粒子上的五重或三重对称轴周围。这些结构表明这些抗体的不同作用机制。

更新日期:2020-07-05
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