Seeking broad protection As scientists develop therapeutic antibodies and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the risk of emergent coronaviruses makes it important to also identify broadly protective antibodies. Wec et al. isolated and characterized hundreds of antibodies against the viral spike protein of SARS-CoV-2 from the memory B cells of a survivor of the 2003 outbreak caused by the related coronavirus, SARS-CoV. In both of these viruses, the spike protein facilitated viral entry by binding to the angiotensin-converting enzyme 2 (ACE2) receptor on human cells. The antibodies targeted multiple sites on the spike protein, but of nine antibodies that showed strong cross-neutralization, eight targeted the domain that binds to ACE2. These eight antibodies also neutralized a bat SARS-related virus. Illuminating the epitopes on the viral spike protein that bind cross-neutralizing antibodies could guide the design of broadly protective vaccines. Science, this issue p. 731 Broadly neutralizing antibodies that target overlapping epitopes on the SARS-CoV-2 spike protein have been isolated. Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.

中文翻译：

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人单克隆抗体广泛中和 SARS 相关病毒


寻求广泛的保护随着科学家开发针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的治疗性抗体和疫苗，新出现的冠状病毒的风险使得识别广泛的保护性抗体也变得很重要。韦克等人。从 2003 年相关冠状病毒 SARS-CoV 爆发的幸存者的记忆 B 细胞中分离并鉴定了数百种针对 SARS-CoV-2 病毒刺突蛋白的抗体。在这两种病毒中，刺突蛋白通过与人类细胞上的血管紧张素转换酶 2 (ACE2) 受体结合来促进病毒进入。这些抗体针对刺突蛋白上的多个位点，但在表现出强交叉中和作用的 9 种抗体中，有 8 种针对与 ACE2 结合的结构域。这八种抗体还中和了蝙蝠SARS相关病毒。阐明病毒刺突蛋白上与交叉中和抗体结合的表位可以指导广泛保护性疫苗的设计。科学，本期第 14 页。 731 已分离出针对 SARS-CoV-2 刺突蛋白上重叠表位的广泛中和抗体。迫切需要针对已知和出现前的人类冠状病毒（HCoV）的广泛保护性疫苗。为了更深入地了解交叉中和抗体反应，我们挖掘了恢复期严重急性呼吸综合征 (SARS) 供体的记忆 B 细胞库，并鉴定了 200 种针对多个保守位点的 SARS 冠状病毒 2 (SARS-CoV-2) 结合抗体位于刺突 (S) 蛋白上。大部分非中和抗体表现出高水平的体细胞超突变，并与循环中的 HCoV 发生交叉反应，这表明对先前 HCoV 感染引起的先前存在的记忆 B 细胞的回忆。 多种抗体通过阻断受体附着和诱导 S1 脱落，有效交叉中和 SARS-CoV、SARS-CoV-2 和蝙蝠 SARS 样病毒 WIV1。这些抗体代表了治疗干预的有希望的候选者，并揭示了泛沙病毒疫苗合理设计的目标。