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A highly potent antibody effective against SARS-CoV-2 variants of concern
Cell Reports ( IF 7.5 ) Pub Date : 2021-09-21 , DOI: 10.1016/j.celrep.2021.109814
Craig Fenwick 1 , Priscilla Turelli 2 , Laurent Perez 1 , Céline Pellaton 1 , Line Esteves-Leuenberger 1 , Alex Farina 1 , Jérémy Campos 1 , Erica Lana 1 , Flurin Fiscalini 1 , Charlène Raclot 2 , Florence Pojer 2 , Kelvin Lau 2 , Davide Demurtas 2 , Marc Descatoire 1 , Victor S Joo 1 , Mathilde Foglierini 1 , Alessandra Noto 1 , Rana Abdelnabi 3 , Caroline S Foo 3 , Laura Vangeel 3 , Johan Neyts 3 , Wenjuan Du 4 , Berend-Jan Bosch 4 , Geertruida Veldman 5 , Pieter Leyssen 3 , Volker Thiel 6 , Roger LeGrand 7 , Yves Lévy 8 , Didier Trono 2 , Giuseppe Pantaleo 9
Affiliation  

Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity to vaccine-induced immunity. Here, we screen B cells from COVID-19 donors and identify P5C3, a highly potent and broadly neutralizing monoclonal antibody with picomolar neutralizing activity against all SARS-CoV-2 variants of concern (VOCs) identified to date. Structural characterization of P5C3 Fab in complex with the spike demonstrates a neutralizing activity defined by a large buried surface area, highly overlapping with the receptor-binding domain (RBD) surface necessary for ACE2 interaction. We further demonstrate that P5C3 shows complete prophylactic protection in the SARS-CoV-2-infected hamster challenge model. These results indicate that P5C3 opens exciting perspectives either as a prophylactic agent in immunocompromised individuals with poor response to vaccination or as combination therapy in SARS-CoV-2-infected individuals.



中文翻译:

一种有效对抗 SARS-CoV-2 变异体的高效抗体

由于病毒变种的传播效率提高、对市售治疗性抗体具有抵抗力以及对疫苗诱导免疫的敏感性降低,对正在进行的 SARS-CoV-2 大流行的控制受到威胁。在这里,我们筛选了来自 COVID-19 供体的 B 细胞,并鉴定了 P5C3,这是一种高效且广泛中和的单克隆抗体,对迄今为止发现的所有 SARS-CoV-2 相关变体 (VOC) 具有皮摩尔中和活性。与刺突复合物中的 P5C3 Fab 的结构表征表明,中和活性由大的埋藏表面积定义,与 ACE2 相互作用所需的受体结合域 (RBD) 表面高度重叠。我们进一步证明 P5C3 在 SARS-CoV-2 感染的仓鼠攻击模型中显示出完整的预防性保护。这些结果表明,P5C3 开启了令人兴奋的前景,无论是作为对疫苗接种反应不佳的免疫功能低下个体的预防剂,还是作为 SARS-CoV-2 感染个体的联合疗法。

更新日期:2021-10-12
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