1区 · 综合性期刊
ArticleOA
作者: Shi, Quan ; Wang, Meiniang ; Liu, Chuanyu ; Yu, Haisheng ; Peng, Xiaofang ; Feng, Chengqian ; Ke, Bixia ; Li, Jiaojiao ; Xiang, Haitao ; Huang, Yaling ; Wang, Yaping ; Liu, Xiaopan ; Guo, Liliangzi ; Ke, Changwen ; Shi, Jingrong ; Hu, Fengyu ; He, Jun ; Wang, Qian ; Li, Feng ; Liu, Longqi ; Zheng, Pingqian ; Tang, Xiaoping ; Tang, Guofang ; Li, Zimu ; Gao, Xijie ; Liang, Dan ; Xiong, Xiaoli ; Zhang, Yudi ; Liu, Banghui ; Xie, Caixia ; Chen, Ling ; Yan, Qihong ; Yang, Naibo ; Hu, Peiyu ; Pei, Rongjuan ; Lin, Xiumei ; Su, Mengzhen ; Chen, Qiuluan ; Chen, Xinwen
Abstract:SARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier in the pandemic. Investigation of memory B cells from patients primarily with breakthrough infections with the Delta variant enables isolation of a number of neutralizing antibodies cross-reactive to heterologous variants of concern (VOCs) including Omicron variants (BA.1-BA.4). Structural studies identify altered complementarity determining region (CDR) amino acids and highly unusual heavy chain CDR2 insertions respectively in two representative cross-neutralizing antibodies—YB9-258 and YB13-292. These features are putatively introduced by somatic hypermutation and they are heavily involved in epitope recognition to broaden neutralization breadth. Previously, insertions/deletions were rarely reported for antiviral antibodies except for those induced by HIV-1 chronic infections. These data provide molecular mechanisms for cross-neutralization of heterologous SARS-CoV-2 variants by antibodies isolated from Delta variant infected patients with implications for future vaccination strategy.
