Inactivated vaccine-elicited potent antibodies can broadly neutralize SARS-CoV-2 circulating variants

Yubin Liu, Ziyi Wang, Xinyu Zhuang, Shengnan Zhang, Zhicheng Chen, Yan Zou, Jie Sheng, Tianpeng Li, Wanbo Tai, Jinfang Yu, Yanqun Wang, Zhaoyong Zhang, Yunfeng Chen, Liangqin Tong, Xi Yu, Linjuan Wu, Dong Chen, Renli Zhang, Ningyi Jin, Weijun Shen (), Jincun Zhao (), Mingyao Tian (), Xinquan Wang () and Gong Cheng ()
Additional contact information
Yubin Liu: Tsinghua University
Ziyi Wang: Tsinghua University
Xinyu Zhuang: Chinese Academy of Agricultural Sciences
Shengnan Zhang: the First Affiliated Hospital of Guangzhou Medical University
Zhicheng Chen: Center for Translational Research, Shenzhen Bay Laboratory
Yan Zou: Shenzhen Bay Laboratory
Jie Sheng: Shenzhen Bay Laboratory
Tianpeng Li: Center for Translational Research, Shenzhen Bay Laboratory
Wanbo Tai: Shenzhen Bay Laboratory
Jinfang Yu: Tsinghua University
Yanqun Wang: the First Affiliated Hospital of Guangzhou Medical University
Zhaoyong Zhang: the First Affiliated Hospital of Guangzhou Medical University
Yunfeng Chen: Shenzhen Bay Laboratory
Liangqin Tong: Tsinghua University
Xi Yu: Tsinghua University
Linjuan Wu: Tsinghua University
Dong Chen: Wenzhou Central Hospital
Renli Zhang: Shenzhen Center for Disease Control and Prevention
Ningyi Jin: Chinese Academy of Agricultural Sciences
Weijun Shen: Center for Translational Research, Shenzhen Bay Laboratory
Jincun Zhao: the First Affiliated Hospital of Guangzhou Medical University
Mingyao Tian: Chinese Academy of Agricultural Sciences
Xinquan Wang: Tsinghua University
Gong Cheng: Tsinghua University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract A full understanding of the inactivated COVID-19 vaccine-mediated antibody responses to SARS-CoV-2 circulating variants will inform vaccine effectiveness and vaccination development strategies. Here, we offer insights into the inactivated vaccine-induced antibody responses after prime-boost vaccination at both the polyclonal and monoclonal levels. We characterized the VDJ sequence of 118 monoclonal antibodies (mAbs) and found that 20 neutralizing mAbs showed varied potency and breadth against a range of variants including XBB.1.5, BQ.1.1, and BN.1. Bispecific antibodies (bsAbs) based on nonoverlapping mAbs exhibited enhanced neutralizing potency and breadth against the most antibody-evasive strains, such as XBB.1.5, BQ.1.1, and BN.1. The passive transfer of mAbs or their bsAb effectively protected female hACE2 transgenic mice from challenge with an infectious Delta or Omicron BA.2 variant. The neutralization mechanisms of these antibodies were determined by structural characterization. Overall, a broad spectrum of potent and distinct neutralizing antibodies can be induced in individuals immunized with the SARS-CoV-2 inactivated vaccine BBIBP-CorV, suggesting the application potential of inactivated vaccines and these antibodies for preventing infection by SARS-CoV-2 circulating variants.

Date: 2023
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DOI: 10.1038/s41467-023-37926-7

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