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Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19

Bao-zhong Zhang, View ORCID ProfileYe-fan Hu, Lin-lei Chen, Yi-gang Tong, Jing-chu Hu, Jian-piao Cai, Kwok-Hung Chan, Ying Dou, Jian Deng, Hua-rui Gong, Chaiyaporn Kuwentrai, Wenjun Li, Xiao-lei Wang, Hin Chu, Cai-hui Su, Ivan Fan-Ngai Hung, Thomas Chung Cheung Yau, Kelvin Kai-Wang To, Kwok Yung Yuen, View ORCID ProfileJian-Dong Huang
doi: https://doi.org/10.1101/2020.04.23.056853
Bao-zhong Zhang
2Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, University Town, Nanshan, Shenzhen, 518055, China
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Ye-fan Hu
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, 3/F, Laboratory Block, 21 Sassoon Road, Hong Kong, China
4Department of Medicine, University of Hong Kong, 4/F Professional Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
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Lin-lei Chen
3Department of Microbiology, University of Hong Kong, 19/F T Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
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Yi-gang Tong
5Beijing Advanced Innovation Centre for Soft Matter Science and Engineering (BAIC-SM), College of Life Science and Technology, Beijing University of Chemical Technology
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Jing-chu Hu
2Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, University Town, Nanshan, Shenzhen, 518055, China
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Jian-piao Cai
3Department of Microbiology, University of Hong Kong, 19/F T Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
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Kwok-Hung Chan
3Department of Microbiology, University of Hong Kong, 19/F T Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
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Ying Dou
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, 3/F, Laboratory Block, 21 Sassoon Road, Hong Kong, China
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Jian Deng
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, 3/F, Laboratory Block, 21 Sassoon Road, Hong Kong, China
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Hua-rui Gong
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, 3/F, Laboratory Block, 21 Sassoon Road, Hong Kong, China
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Chaiyaporn Kuwentrai
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, 3/F, Laboratory Block, 21 Sassoon Road, Hong Kong, China
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Wenjun Li
2Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, University Town, Nanshan, Shenzhen, 518055, China
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Xiao-lei Wang
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, 3/F, Laboratory Block, 21 Sassoon Road, Hong Kong, China
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Hin Chu
3Department of Microbiology, University of Hong Kong, 19/F T Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
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Cai-hui Su
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, 3/F, Laboratory Block, 21 Sassoon Road, Hong Kong, China
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Ivan Fan-Ngai Hung
4Department of Medicine, University of Hong Kong, 4/F Professional Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
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Thomas Chung Cheung Yau
4Department of Medicine, University of Hong Kong, 4/F Professional Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
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  • For correspondence: jdhuang@hku.hk
Kelvin Kai-Wang To
3Department of Microbiology, University of Hong Kong, 19/F T Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
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  • For correspondence: jdhuang@hku.hk
Kwok Yung Yuen
3Department of Microbiology, University of Hong Kong, 19/F T Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
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  • For correspondence: jdhuang@hku.hk
Jian-Dong Huang
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, 3/F, Laboratory Block, 21 Sassoon Road, Hong Kong, China
2Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, University Town, Nanshan, Shenzhen, 518055, China
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  • ORCID record for Jian-Dong Huang
  • For correspondence: jdhuang@hku.hk
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Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic is a serious threat to global public health, and imposes severe burdens on the entire human society. The severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) can cause severe respiratory illness and death. Currently, there are no specific antiviral drugs that can treat COVID-19. Several vaccines against SARS-CoV-2 are being actively developed by research groups around the world. The surface S (spike) protein and the highly expressed internal N (nucleocapsid) protein of SARS-CoV-2 are widely considered as promising candidates for vaccines. In order to guide the design of an effective vaccine, we need experimental data on these potential epitope candidates. In this study, we mapped the immunodominant (ID) sites of S protein using sera samples collected from recently discharged COVID-19 patients. The SARS-CoV-2 S protein-specific antibody levels in the sera of recovered COVID-19 patients were strongly correlated with the neutralising antibody titres. We used epitope mapping to determine the landscape of ID sites of S protein, which identified nine linearized B cell ID sites. Four out of the nine ID sites were found in the receptor-binding domain (RBD). Further analysis showed that these ID sites are potential high-affinity SARS-CoV-2 antibody binding sites. Peptides containing two out of the nine sites were tested as vaccine candidates against SARS-CoV-2 in a mouse model. We detected epitope-specific antibodies and SARS-CoV-2-neutralising activity in the immunised mice. This study for the first time provides human serological data for the design of vaccines against COVID-19.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 27, 2020.
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Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19
Bao-zhong Zhang, Ye-fan Hu, Lin-lei Chen, Yi-gang Tong, Jing-chu Hu, Jian-piao Cai, Kwok-Hung Chan, Ying Dou, Jian Deng, Hua-rui Gong, Chaiyaporn Kuwentrai, Wenjun Li, Xiao-lei Wang, Hin Chu, Cai-hui Su, Ivan Fan-Ngai Hung, Thomas Chung Cheung Yau, Kelvin Kai-Wang To, Kwok Yung Yuen, Jian-Dong Huang
bioRxiv 2020.04.23.056853; doi: https://doi.org/10.1101/2020.04.23.056853
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Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19
Bao-zhong Zhang, Ye-fan Hu, Lin-lei Chen, Yi-gang Tong, Jing-chu Hu, Jian-piao Cai, Kwok-Hung Chan, Ying Dou, Jian Deng, Hua-rui Gong, Chaiyaporn Kuwentrai, Wenjun Li, Xiao-lei Wang, Hin Chu, Cai-hui Su, Ivan Fan-Ngai Hung, Thomas Chung Cheung Yau, Kelvin Kai-Wang To, Kwok Yung Yuen, Jian-Dong Huang
bioRxiv 2020.04.23.056853; doi: https://doi.org/10.1101/2020.04.23.056853

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