Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants

Haisheng Yu (), Banghui Liu, Yudi Zhang, Xijie Gao, Qian Wang, Haitao Xiang, Xiaofang Peng, Caixia Xie, Yaping Wang, Peiyu Hu, Jingrong Shi, Quan Shi, Pingqian Zheng, Chengqian Feng, Guofang Tang, Xiaopan Liu, Liliangzi Guo, Xiumei Lin, Jiaojiao Li, Chuanyu Liu, Yaling Huang, Naibo Yang, Qiuluan Chen, Zimu Li, Mengzhen Su, Qihong Yan, Rongjuan Pei, Xinwen Chen, Longqi Liu, Fengyu Hu, Dan Liang, Bixia Ke, Changwen Ke (), Feng Li (), Jun He (), Meiniang Wang (), Ling Chen (), Xiaoli Xiong () and Xiaoping Tang ()
Additional contact information
Haisheng Yu: Guangzhou Medical University
Banghui Liu: the Chinese Academy of Sciences
Yudi Zhang: the Chinese Academy of Sciences
Xijie Gao: Bioland Laboratory (Guangzhou Regenerative Medicine and Health—Guangdong Laboratory)
Qian Wang: the First Affiliated Hospital of Guangzhou Medical University
Haitao Xiang: BGI-Shenzhen
Xiaofang Peng: Guangdong Provincial Center for Disease Control and Prevention
Caixia Xie: BGI-Shenzhen
Yaping Wang: Guangzhou Medical University
Peiyu Hu: Bioland Laboratory (Guangzhou Regenerative Medicine and Health—Guangdong Laboratory)
Jingrong Shi: Guangzhou Medical University
Quan Shi: BGI-Shenzhen
Pingqian Zheng: Bioland Laboratory (Guangzhou Regenerative Medicine and Health—Guangdong Laboratory)
Chengqian Feng: Guangzhou Medical University
Guofang Tang: Guangzhou Medical University
Xiaopan Liu: BGI-Shenzhen
Liliangzi Guo: Guangzhou Medical University
Xiumei Lin: BGI-Shenzhen
Jiaojiao Li: Guangzhou Medical University
Chuanyu Liu: BGI-Shenzhen
Yaling Huang: BGI-Shenzhen
Naibo Yang: BGI-Shenzhen
Qiuluan Chen: Bioland Laboratory (Guangzhou Regenerative Medicine and Health—Guangdong Laboratory)
Zimu Li: the Chinese Academy of Sciences
Mengzhen Su: the Chinese Academy of Sciences
Qihong Yan: the Chinese Academy of Sciences
Rongjuan Pei: Chinese Academy of Sciences
Xinwen Chen: Guangzhou International Bio Island
Longqi Liu: BGI-Shenzhen
Fengyu Hu: Guangzhou Medical University
Dan Liang: Guangdong Provincial Center for Disease Control and Prevention
Bixia Ke: Guangdong Provincial Center for Disease Control and Prevention
Changwen Ke: Guangdong Provincial Center for Disease Control and Prevention
Feng Li: Guangzhou Medical University
Jun He: the Chinese Academy of Sciences
Meiniang Wang: BGI-Shenzhen
Ling Chen: Guangzhou Medical University
Xiaoli Xiong: the Chinese Academy of Sciences
Xiaoping Tang: Guangzhou Medical University

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36761-0

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