研究鉴定出高效的新冠病毒中和人源抗体
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研究鉴定出高效的新冠病毒中和人源抗体

浏览次数:    时间:2020-07-19

本期文章:《自然》:Online/在线发表

美国范德比尔特大学医学中心James E. Crowe Jr、Robert H. Carnahan等研究人员合作鉴定出高效的新冠病毒中和人源抗体。这一研究成果发表于2020年7月15日在线发表在《自然》上。

从一大批靶向突刺(S)糖蛋白的人单克隆抗体(mAb)中,研究人员鉴定出几种具有有效中和活性并完全阻断S受体结合域(S RBD)与人ACE2(hACE2)相互作用的抗体。竞争结合、结构和功能研究将mAb聚类为识别S RBD上不同的表位以及S三聚体不同构象状态的类别。

 

通过识别非重叠位点,COV2-2196和COV2-2130两种有效中和单克隆抗体能够同时与S结合,并协同中和了SARS-CoV-2病毒。在SARS-CoV-2感染的两种小鼠模型中,仅COV2-2196或COV2-2130或两种mAb的组合的被动接种都可以保护小鼠免于体重丢失,并减少病毒载量和肺部炎症。

 

此外,两种最有效的ACE2封闭性单克隆抗体(COV2-2196或COV2-2381)中任意一种的被动接种均可以保护猕猴免受SARS-CoV-2感染。这些结果确定了S RBD上的保护性表位,并为疫苗设计和免疫疗法提供了结构框架。

 

据介绍,COVID-19大流行是对全球健康的主要威胁,对此,医疗手段有限。此外,人们目前对体液免疫的机制还缺乏透彻的了解。

 

附:英文原文

Title: Potently neutralizing and protective human antibodies against SARS-CoV-2

Author: Seth J. Zost, Pavlo Gilchuk, James Brett Case, Elad Binshtein, Rita E. Chen, Joseph P. Nkolola, Alexandra Schfer, Joseph X. Reidy, Andrew Trivette, Rachel S. Nargi, Rachel E. Sutton, Naveenchandra Suryadevara, David R. Martinez, Lauren E. Williamson, Elaine C. Chen, Taylor Jones, Samuel Day, Luke Myers, Ahmed O. Hassan, Natasha M. Kafai, Emma S. Winkler, Julie M. Fox, Swathi Shrihari, Benjamin K. Mueller, Jens Meiler, Abishek Chandrashekar, Noe B. Mercado, James J. Steinhardt, Kuishu Ren, Yueh-Ming Loo, Nicole L. Kallewaard, Broc T. McCune, Shamus P. Keeler, Michael J. Holtzman, Dan H. Barouch, Lisa E. Gralinski, Ralph S. Baric, Larissa B. Thackray, Michael S. Diamond, Robert H. Carnahan, James E. Crowe

Issue&Volume: 2020-07-15

Abstract: The COVID-19 pandemic is a major threat to global health1 for which there are limited medical countermeasures2,3. Moreover, we currently lack a thorough understanding of mechanisms of humoral immunity4. From a larger panel of human monoclonal antibodies (mAbs) targeting the spike (S) glycoprotein5, we identified several that exhibited potent neutralizing activity and fully blocked the receptor-binding domain of S (SRBD) from interacting with human ACE2 (hACE2). Competition-binding, structural, and functional studies allowed clustering of the mAbs into classes recognizing distinct epitopes on the SRBD as well as distinct conformational states of the S trimer. Potent neutralizing mAbs recognizing non-overlapping sites, COV2-2196 and COV2-2130, bound simultaneously to S and synergistically neutralized authentic SARS-CoV-2 virus. In two mouse models of SARS-CoV-2 infection, passive transfer of either COV2-2196 or COV2-2130 alone or a combination of both mAbs protected mice from weight loss and reduced viral burden and inflammation in the lung. In addition, passive transfer of each of two of the most potently ACE2 blocking mAbs (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection. These results identify protective epitopes on SRBD and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutics.

DOI: 10.1038/s41586-020-2548-6

Source: https://www.nature.com/articles/s41586-020-2548-6

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
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