ジャーナル: Cell Rep / 年: 2022 タイトル: Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents. 著者: Yunlong Cao / Fanchong Jian / Zhiying Zhang / Ayijiang Yisimayi / Xiaohua Hao / Linlin Bao / Fei Yuan / Yuanling Yu / Shuo Du / Jing Wang / Tianhe Xiao / Weiliang Song / Ying Zhang / Pulan ...著者: Yunlong Cao / Fanchong Jian / Zhiying Zhang / Ayijiang Yisimayi / Xiaohua Hao / Linlin Bao / Fei Yuan / Yuanling Yu / Shuo Du / Jing Wang / Tianhe Xiao / Weiliang Song / Ying Zhang / Pulan Liu / Ran An / Peng Wang / Yao Wang / Sijie Yang / Xiao Niu / Yuhang Zhang / Qingqing Gu / Fei Shao / Yaling Hu / Weidong Yin / Aihua Zheng / Youchun Wang / Chuan Qin / Ronghua Jin / Junyu Xiao / Xiaoliang Sunney Xie / 要旨: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves that previous NAb drug screening strategies are deficient against the fast-evolving SARS-CoV-2. Better broad NAb drug candidate selection methods are needed. Here, we describe a rational approach for identifying RBD-targeting broad SARS-CoV-2 NAb cocktails. Based on high-throughput epitope determination, we propose that broad NAb drugs should target non-immunodominant RBD epitopes to avoid herd-immunity-directed escape mutations. Also, their interacting antigen residues should focus on sarbecovirus conserved sites and associate with critical viral functions, making the antibody-escaping mutations less likely to appear. Following these criteria, a featured non-competing antibody cocktail, SA55+SA58, is identified from a large collection of broad sarbecovirus NAbs isolated from SARS-CoV-2-vaccinated SARS convalescents. SA55+SA58 potently neutralizes ACE2-utilizing sarbecoviruses, including circulating Omicron variants, and could serve as broad SARS-CoV-2 prophylactics to offer long-term protection, especially for individuals who are immunocompromised or with high-risk comorbidities.