Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
National Centre for Infectious Diseases, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, Lee Kong Chian School of Medicine, 16 Jalan Tan Tock Seng, Singapore 308442, Singapore.
Science. 2020 Aug 21;369(6506):1010-1014. doi: 10.1126/science.abd0827. Epub 2020 Jun 15.
Neutralizing antibodies have become an important tool in treating infectious diseases. Recently, two separate approaches yielded successful antibody treatments for Ebola-one from genetically humanized mice and the other from a human survivor. Here, we describe parallel efforts using both humanized mice and convalescent patients to generate antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, which yielded a large collection of fully human antibodies that were characterized for binding, neutralization, and three-dimensional structure. On the basis of these criteria, we selected pairs of highly potent individual antibodies that simultaneously bind the receptor binding domain of the spike protein, thereby providing ideal partners for a therapeutic antibody cocktail that aims to decrease the potential for virus escape mutants that might arise in response to selective pressure from a single-antibody treatment.
中和抗体已成为治疗传染病的重要工具。最近,两种不同的方法成功地从基因人源化小鼠和一位康复患者中获得了埃博拉病毒的抗体治疗方法。在这里,我们描述了使用人源化小鼠和康复患者的平行研究,以产生针对严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)刺突蛋白的抗体,从而产生了大量的完全人源化抗体,这些抗体的结合、中和和三维结构进行了表征。基于这些标准,我们选择了一对高活性的单克隆抗体,它们同时结合刺突蛋白的受体结合域,从而为旨在降低潜在病毒逃逸突变体的治疗性抗体鸡尾酒提供了理想的组合,这些突变体可能是由于对单一抗体治疗的选择压力而产生的。