小柯机器人

科学家开发出一种能够广泛中和sarbecovirus的人类单克隆抗体
2021-07-25 12:15

瑞士Vir生物技术公司Matteo Samuele Pizzuto等研究人员合作开发出一种能够广泛中和sarbecovirus的人类单克隆抗体。2021年7月19日,《自然》杂志在线发表了这项成果。

研究人员描述了一种人类单克隆抗体(mAb),命名为S2X259,它能识别一个高度保守的隐性受体结合域(RBD)表位,并与所有sarbecovirus病毒支系的突刺蛋白发生交叉反应。S2X259通过抑制ACE2与RBD的结合,广泛地中和SARS-CoV-2包括B.1.1.7、B.1.351、P.1、B.1.427/B.1.429担忧变异体(VOC)以及广泛的人类和潜在的人畜共患sarbecovirus病毒的突刺进入。此外,深度突变扫描和体外逃逸选择实验证明,S2X259拥有的逃逸特征仅限于单一的替代物G504D。

结果表明,S2X259的预防性和治疗性给药可以保护叙利亚仓鼠免受原型SARS-CoV-2和B.1.351 VOC的挑战,表明这种mAb是预防和治疗突发变种和人畜共患感染的有希望的候选药物。这些数据揭示了广义中和抗体所针对的一个关键抗原位点,并将指导泛sarbecovirus病毒疫苗的设计。

据介绍,最近,SARS-CoV-2 VOC和冠状病毒在人类群体中反复传播突出了对广义中和抗体的需求,这种抗体不受正在发生的抗原漂移的影响,可以预防或治疗未来的人畜共患感染。

附:英文原文

Title: Broad sarbecovirus neutralization by a human monoclonal antibody

Author: M. Alejandra Tortorici, Nadine Czudnochowski, Tyler N. Starr, Roberta Marzi, Alexandra C. Walls, Fabrizia Zatta, John E. Bowen, Stefano Jaconi, Julia Di Iulio, Zhaoqian Wang, Anna De Marco, Samantha K. Zepeda, Dora Pinto, Zhuoming Liu, Martina Beltramello, Istvan Bartha, Michael P. Housley, Florian A. Lempp, Laura E. Rosen, Exequiel Dellota, Hannah Kaiser, Martin Montiel-Ruiz, Jiayi Zhou, Amin Addetia, Barbara Guarino, Katja Culap, Nicole Sprugasci, Christian Saliba, Eneida Vetti, Isabella Giacchetto-Sasselli, Chiara Silacci Fregni, Rana Abdelnabi, Shi-Yan Caroline Foo, Colin Havenar-Daughton, Michael A. Schmid, Fabio Benigni, Elisabetta Cameroni, Johan Neyts, Amalio Telenti, Herbert W. Virgin, Sean P. J. Whelan, Gyorgy Snell, Jesse D. Bloom, Davide Corti, David Veesler, Matteo Samuele Pizzuto

Issue&Volume: 2021-07-19

Abstract: The recent emergence of SARS-CoV-2 variants of concern (VOC)1–10 and the recurrent spillovers of coronaviruses11,12 in 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 (mAb), designated S2X259, recognizing a highly conserved cryptic receptor-binding domain (RBD) epitope and cross-reacting with spikes from all sarbecovirus clades. S2X259 broadly neutralizes spike-mediated entry of SARS-CoV-2 including the B.1.1.7, B.1.351, P.1, B.1.427/B.1.429 VOC, as well as a wide spectrum of human and potentially zoonotic sarbecoviruses through inhibition of ACE2 binding to the RBD. Furthermore, deep-mutational scanning and in vitro escape selection experiments demonstrate that S2X259 possesses an escape profile limited to the single substitution G504D. We show that prophylactic and therapeutic administration of S2X259 protects Syrian hamsters against challenge with the prototypic SARS-CoV-2 and the B.1.351 VOC, suggesting this mAb is a promising candidate for the prevention and treatment of emergent variants and zoonotic infections. Our data unveil a key antigenic site targeted by broadly-neutralizing antibodies and will guide the design of pan-sarbecovirus vaccines.

DOI: 10.1038/s41586-021-03817-4

Source: https://www.nature.com/articles/s41586-021-03817-4

 

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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