Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model
Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model
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DOI：
10.1126/science.abc7520
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发表时间：
2020-08-21
期刊：
影响因子：
56.9
通讯作者：
Burton, Dennis R.
中科院分区：
文献类型：
--
作者：
Rogers, Thomas F.;Zhao, Fangzhu;Burton, Dennis R.
预防和治疗冠状病毒病的对策2019年(新冠肺炎)是全球卫生优先事项。我们招募了一组严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)康复的参与者，开发了中和试验来研究抗体反应，采用了我们的高通量抗体生成管道来快速筛选1800多种抗体，并建立了动物模型来测试保护作用。我们分离了针对受体结合域(RBD)上的两个表位和针对SPEKE(S)蛋白上不同的非RBD表位的有效中和抗体(NAB)。治疗动物的维持体重和低肺病毒滴度表明，被动转移NAB对叙利亚仓鼠在高剂量SARS-CoV-2攻击中的疾病具有保护作用。这项研究表明，NABS在预防和潜在治疗新冠肺炎方面可能起到了作用。NAB还定义了保护性表位，以指导疫苗设计。
Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.