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Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion

Can Yue, Weiliang Song, Lei Wang, Fanchong Jian, Xiaosu Chen, Fei Gao, Zhongyang Shen, Youchun Wang, Xiangxi Wang, Yunlong Cao
doi: https://doi.org/10.1101/2023.01.03.522427
Can Yue
1CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, P.R. China
2Changping Laboratory, Beijing, P.R. China
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Weiliang Song
2Changping Laboratory, Beijing, P.R. China
3Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China
4School of Life Sciences, Peking University, Beijing, P.R. China
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Lei Wang
1CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, P.R. China
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Fanchong Jian
1CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, P.R. China
2Changping Laboratory, Beijing, P.R. China
5College of Chemistry and Molecular Engineering, Peking University, Beijing, P.R. China
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Xiaosu Chen
6Frontier Research Center for Cell Response, Institute of Immunology, College of Life Sciences, Nankai University, Tianjin 300071, China
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Fei Gao
7Department of Pulmonary and Critical Care Medicine, The Fourth Hospital of Inner Mongolia, Hohhot 010058, China
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Zhongyang Shen
8Organ Transplant Center, NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, Nankai University, Tianjin 300192, China
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Youchun Wang
2Changping Laboratory, Beijing, P.R. China
9Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, P.R. China
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Xiangxi Wang
1CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, P.R. China
2Changping Laboratory, Beijing, P.R. China
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  • For correspondence: xiangxi@ibp.ac.cn yunlongcao@pku.edu.cn
Yunlong Cao
2Changping Laboratory, Beijing, P.R. China
3Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China
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  • For correspondence: xiangxi@ibp.ac.cn yunlongcao@pku.edu.cn
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Abstract

SARS-CoV-2 recombinant subvariant XBB.1.5 is growing rapidly in the United States, carrying an additional Ser486Pro substitution compared to XBB.1 and outcompeting BQ.1.1 and other XBB sublineages. The underlying mechanism for such high transmissibility remains unclear. Here we show that XBB.1.5 exhibits a substantially higher hACE2-binding affinity compared to BQ.1.1 and XBB/XBB.1. Convalescent plasma samples from BA.1, BA.5, and BF.7 breakthrough infection are significantly evaded by both XBB.1 and XBB.1.5, with XBB.1.5 displaying slightly weaker immune evasion capability than XBB.1. Evusheld and Bebtelovimab could not neutralize XBB.1/XBB.1.5, while Sotrovimab remains its weak reactivity and notably, SA55 is still highly effective. The fact that XBB.1 and XBB.1.5 showed comparable antibody evasion but distinct transmissibility suggests enhanced receptor-binding affinity would indeed lead to higher growth advantages. The strong hACE2 binding of XBB.1.5 could also enable its tolerance of further immune escape mutations, which should be closely monitored.

Competing Interest Statement

Y.C. is a co-founder of Singlomics Biopharmaceuticals and inventor of provisional patents associated with SARS-CoV-2 neutralizing antibodies, including SA55 and SA58. All other authors declare no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 03, 2023.
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Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion
Can Yue, Weiliang Song, Lei Wang, Fanchong Jian, Xiaosu Chen, Fei Gao, Zhongyang Shen, Youchun Wang, Xiangxi Wang, Yunlong Cao
bioRxiv 2023.01.03.522427; doi: https://doi.org/10.1101/2023.01.03.522427
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Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion
Can Yue, Weiliang Song, Lei Wang, Fanchong Jian, Xiaosu Chen, Fei Gao, Zhongyang Shen, Youchun Wang, Xiangxi Wang, Yunlong Cao
bioRxiv 2023.01.03.522427; doi: https://doi.org/10.1101/2023.01.03.522427

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