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Broad sarbecovirus neutralization by a human monoclonal antibody

机译：通过人单克隆抗体中和宽的Sarbec病毒

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The recent emergence of SARS-CoV-2 variants of concern(1-10) and the recurrent spillovers of coronaviruses(11,12) into the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here we describe a human monoclonal antibody designated S2X259, which recognizes a highly conserved cryptic epitope of the receptor-binding domain and cross-reacts with spikes from all clades of sarbecovirus. S2X259 broadly neutralizes spike-mediated cell entry of SARS-CoV-2, including variants of concern (B.1.1.7, B.1.351, P.1, and B.1.427/B.1.429), as well as a wide spectrum of human and potentially zoonotic sarbecoviruses through inhibition of angiotensin-converting enzyme 2 (ACE2) binding to the receptor-binding domain. Furthermore, deep-mutational scanning and in vitro escape selection experiments demonstrate that S2X259 possesses an escape profile that is limited to a single substitution, G504D. We show that prophylactic and therapeutic administration of S2X259 protects Syrian hamsters (Mesocricetus auratus) against challenge with the prototypic SARS-CoV-2 and the B.1.351 variant of concern, which suggests that this monoclonal antibody is a promising candidate for the prevention and treatment of emergent variants and zoonotic infections. Our data reveal a key antigenic site that is targeted by broadly neutralizing antibodies and will guide the design of vaccines that are effective against all sarbecoviruses.
机译：最近的SARS-COV-2变异的出现（1-10）和冠状病毒（11,12）的复发溢出渗透到人口中的突显强调了对不受持续的抗原漂移影响的宽度中和抗体的需要可以预防或治疗未来的动物区感染。在这里，我们描述了指定的S2X259的人单克隆抗体，其识别受体结合结构域的高度保守的隐秘表位，并与来自Sarbecovirus的所有枝条的尖峰交叉反应。 S2X259广泛中和SARS-COV-2的穗状体介导的细胞入口，包括关注的变体（B.1.1.7，B.1.351，P.1和B.1.427 / B.1.429），以及广谱通过抑制血管紧张素转换酶2（ACE2）与受体结合结构域结合的人和可能的人群伤害。此外，深突扫描和体外逃逸选择实验表明S2X259具有逃逸轮廓，其限于单个替换，G504D。我们显示S2X259的预防性和治疗施用保护叙利亚仓鼠（Mesocricetus Auratus）与原型SARS-COV-2和令人担忧的B.1.351变异的攻击，这表明这种单克隆抗体是预防和治疗的有希望的候选者突出变异性和动物园感染。我们的数据揭示了一种键抗原位点，其是通过宽度中和抗体来靶向，并指导疫苗的设计，这些疫苗对所有SARBec病毒有效。

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