Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants

Yanqun Wang, An Yan, Deyong Song, Maoqin Duan, Chuangchuang Dong, Jiantao Chen, Zihe Jiang, Yuanzhu Gao, Muding Rao, Jianxia Feng, Zhaoyong Zhang, Ruxi Qi, Xiaomin Ma, Hong Liu, Beibei Yu, Qiaoping Wang, Mengqi Zong, Jie Jiao, Pingping Xing, Rongrong Pan, Dan Li, Juxue Xiao, Junbo Sun, Ying Li, Linfeng Zhang, Zhenduo Shen, Baiping Sun, Yanyan Zhao, Lu Zhang, Jun Dai, Jingxian Zhao, Lan Wang (), Changlin Dou (), Zheng Liu () and Jincun Zhao ()
Additional contact information
Yanqun Wang: the First Affiliated Hospital of Guangzhou Medical University
An Yan: Southern University of Science and Technology
Deyong Song: Shandong Boan Biotechnology Co., Ltd.
Maoqin Duan: National Institutes for Food and Drug Control (NIFDC)
Chuangchuang Dong: Shandong Boan Biotechnology Co., Ltd.
Jiantao Chen: the First Affiliated Hospital of Guangzhou Medical University
Zihe Jiang: Southern University of Science and Technology
Yuanzhu Gao: Southern University of Science and Technology
Muding Rao: Shandong Boan Biotechnology Co., Ltd.
Jianxia Feng: Shandong Boan Biotechnology Co., Ltd.
Zhaoyong Zhang: the First Affiliated Hospital of Guangzhou Medical University
Ruxi Qi: Southern University of Science and Technology
Xiaomin Ma: Southern University of Science and Technology
Hong Liu: Shandong Boan Biotechnology Co., Ltd.
Beibei Yu: Shandong Boan Biotechnology Co., Ltd.
Qiaoping Wang: Shandong Boan Biotechnology Co., Ltd.
Mengqi Zong: Shandong Boan Biotechnology Co., Ltd.
Jie Jiao: Shandong Boan Biotechnology Co., Ltd.
Pingping Xing: Shandong Boan Biotechnology Co., Ltd.
Rongrong Pan: Shandong Boan Biotechnology Co., Ltd.
Dan Li: Shandong Boan Biotechnology Co., Ltd.
Juxue Xiao: the First Affiliated Hospital of Guangzhou Medical University
Junbo Sun: Shandong Boan Biotechnology Co., Ltd.
Ying Li: Shandong Boan Biotechnology Co., Ltd.
Linfeng Zhang: Shandong Boan Biotechnology Co., Ltd.
Zhenduo Shen: Shandong Boan Biotechnology Co., Ltd.
Baiping Sun: Shandong Boan Biotechnology Co., Ltd.
Yanyan Zhao: Shandong Boan Biotechnology Co., Ltd.
Lu Zhang: Guangzhou Customs District Technology Centre
Jun Dai: Guangzhou Customs District Technology Centre
Jingxian Zhao: the First Affiliated Hospital of Guangzhou Medical University
Lan Wang: National Institutes for Food and Drug Control (NIFDC)
Changlin Dou: Shandong Boan Biotechnology Co., Ltd.
Zheng Liu: Southern University of Science and Technology
Jincun Zhao: the First Affiliated Hospital of Guangzhou Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. Here, we identify a highly conserved neutralizing epitope targeted by a broad-spectrum neutralizing antibody BA7535, which demonstrates high neutralization potency against not only previous variants, such as Alpha, Beta, Gamma, Delta and Omicron BA.1-BA.5, but also more recently emerged Omicron subvariants, including BF.7, CH.1.1, XBB.1, XBB.1.5, XBB.1.9.1, EG.5. Structural analysis of the Omicron Spike trimer with BA7535-Fab using cryo-EM indicates that BA7535 recognizes a highly conserved cryptic receptor-binding domain (RBD) epitope, avoiding most of the mutational hot spots in RBD. Furthermore, structural simulation based on the interaction of BA7535-Fab/RBD complexes dissects the broadly neutralizing effect of BA7535 against latest variants. Therapeutic and prophylactic treatment with BA7535 alone or in combination with BA7208 protected female mice from the circulating Omicron BA.5 and XBB.1 variant infection, suggesting the highly conserved neutralizing epitope serves as a potential target for developing highly potent therapeutic antibodies and vaccines.

Date: 2024
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DOI: 10.1038/s41467-024-45050-3

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