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科学家发现一种治疗性非自我反应型SARS-CoV-2抗体
作者：小柯机器人 发布时间：2020/9/25 9:33:03

德国柏林大学Harald Prüss、Jakob Kreye等研究人员合作发现一种治疗性非自我反应型SARS-CoV-2抗体，可防止COVID-19仓鼠模型中的肺部疾病。该研究于2020年9月23日在线发表于国际一流学术期刊《细胞》。

在来自十名COVID-19患者的598种人类单克隆抗体（mAb）中，研究人员鉴定出40种强效中和mAb。最有效的mAb CV07-209中和了真实的SARS-CoV-2，其IC50为3.1ng/ml。与SARS-CoV-2受体结合域位于2.55和2.70Å处复合的两个mAb晶体结构揭示了ACE2附着的直接阻断。有趣的是，一些近种系的SARS-CoV-2中和单克隆抗体与哺乳动物自身抗原发生了反应。CV07-209保护仓鼠免受SARS-CoV-2感染、体重减轻和肺部病理。
 
这些结果表明，SARS-CoV-2感染期间引起的非自反应性病毒中和单克隆抗体是有前景的治疗策略。
 
据了解，SARS-CoV-2的出现导致了COVID-19的大流行，其表现为呼吸道症状和多器官功能障碍。目前需要详细描述病毒中和抗体和目标表位的特征，进而了解COVID-19的病理生理学并指导免疫策略。
 
附：英文原文

Title: A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model

Author: Jakob Kreye, S. Momsen Reincke, Hans-Christian Kornau, Elisa Sánchez-Sendin, Victor Max Corman, Hejun Liu, Meng Yuan, Nicholas C. Wu, Xueyong Zhu, Chang-Chun D. Lee, Jakob Trimpert, Markus Hltje, Kristina Dietert, Laura Stffler, Niels von Wardenburg, Scott van Hoof, Marie A. Homeyer, Julius Hoffmann, Azza Abdelgawad, Achim D. Gruber, Luca D. Bertzbach, Daria Vladimirova, Lucie Y. Li, Paula Charlotte Barthel, Karl Skriner, Andreas C. Hocke, Stefan Hippenstiel, Martin Witzenrath, Norbert Suttorp, Florian Kurth, Christiana Franke, Matthias Endres, Dietmar Schmitz, Lara Maria Jeworowski, Anja Richter, Marie Luisa Schmidt, Tatjana Schwarz, Marcel Alexander Müller, Christian Drosten, Daniel Wendisch, Leif E. Sander, Nikolaus Osterrieder, Ian A. Wilson, Harald Prüss

Issue&Volume: 2020-09-23

Abstract: The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC50 of 3.1 ng/ml. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2 neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.

DOI: 10.1016/j.cell.2020.09.049

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31246-0

期刊信息
Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：36.216
官方网址：https://www.cell.com/