Protective neutralizing antibodies Antibodies produced by survivors of coronavirus disease 2019 (COVID-19) may be leveraged to develop therapies. A first step is identifying neutralizing antibodies, which confer strong protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rogers et al. used a high-throughput pipeline to isolate and characterize monoclonal antibodies from convalescent donors. Antibodies were selected for binding to the viral spike protein, which facilitates entry into host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Most isolated antibodies bound to regions of the spike outside of the receptor binding domain (RBD); however, a larger proportion of the RBD-binding antibodies were neutralizing, with the most potent binding at a site that overlaps the ACE2 binding site. Two of the neutralizing antibodies were tested in Syrian hamsters and provided protection against SARS-CoV-2 infection. Science, this issue p. 956 Passive transfer of a neutralizing antibody provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. 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.

中文翻译：

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在小动物模型中分离强效 SARS-CoV-2 中和抗体并预防疾病


保护性中和抗体 2019 年冠状病毒病 (COVID-19) 幸存者产生的抗体可用于开发治疗方法。第一步是识别中和抗体，该抗体可针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 提供强有力的保护。罗杰斯等人。使用高通量管道来分离和表征来自恢复期供体的单克隆抗体。选择与病毒刺突蛋白结合的抗体，该蛋白通过与血管紧张素转换酶 2 (ACE2) 受体结合，促进进入宿主细胞。大多数分离的抗体与受体结合域 (RBD) 之外的刺突区域结合；然而，大部分 RBD 结合抗体具有中和作用，其中与 ACE2 结合位点重叠的位点具有最强的结合力。其中两种中和抗体在叙利亚仓鼠中进行了测试，并提供了针对 SARS-CoV-2 感染的保护作用。科学，本期第 14 页。 956 中和抗体的被动转移为叙利亚仓鼠在高剂量 SARS-CoV-2 攻击中提供了针对疾病的保护。预防和治疗 2019 年冠状病毒病 (COVID-19) 的对策是全球卫生优先事项。我们招募了一批严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 康复的参与者，开发了中和测定法来研究抗体反应，调整我们的高通量抗体生成管道以快速筛选 1800 多种抗体，并建立了动物模型模型来测试保护。我们分离了针对受体结合域 (RBD) 上的两个表位以及刺突 (S) 蛋白上不同的非 RBD 表位的强效中和抗体 (nAb)。 经治疗的动物体重保持不变且肺部病毒滴度较低，表明 nAb 的被动转移为叙利亚仓鼠在高剂量 SARS-CoV-2 攻击中提供了针对疾病的保护。该研究表明 nAb 在预防和潜在治疗 COVID-19 中发挥作用。 nAb 还定义了保护性表位来指导疫苗设计。