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Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine

View ORCID ProfileYangtao Wu, Xiaofen Huang, Lunzhi Yuan, Shaojuan Wang, Yali Zhang, Hualong Xiong, Rirong Chen, Jian Ma, Ruoyao Qi, Meifeng Nie, Jingjing Xu, Zhigang Zhang, Liqiang Chen, Min Wei, Ming Zhou, Minping Cai, Yang Shi, Liang Zhang, Huan Yu, Junping Hong, Zikang Wang, Yunda Hong, Mingxi Yue, Zonglin Li, Dabing Chen, Qingbing Zheng, Shaowei Li, Yixin Chen, Tong Cheng, Jun Zhang, Tianying Zhang, Huachen Zhu, Qinjian Zhao, Quan Yuan, Yi Guan, View ORCID ProfileNingshao Xia
doi: https://doi.org/10.1101/2020.12.18.423552
Yangtao Wu
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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  • ORCID record for Yangtao Wu
Xiaofen Huang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Lunzhi Yuan
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Shaojuan Wang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Yali Zhang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Hualong Xiong
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Rirong Chen
2State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, P. R. China
3Joint Institute of Virology (Shantou University and The University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, P. R. China
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Jian Ma
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Ruoyao Qi
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Meifeng Nie
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Jingjing Xu
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Zhigang Zhang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Liqiang Chen
2State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, P. R. China
3Joint Institute of Virology (Shantou University and The University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, P. R. China
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Min Wei
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Ming Zhou
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Minping Cai
2State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, P. R. China
3Joint Institute of Virology (Shantou University and The University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, P. R. China
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Yang Shi
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Liang Zhang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Huan Yu
2State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, P. R. China
3Joint Institute of Virology (Shantou University and The University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, P. R. China
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Junping Hong
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Zikang Wang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Yunda Hong
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Mingxi Yue
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Zonglin Li
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Dabing Chen
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Qingbing Zheng
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Shaowei Li
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Yixin Chen
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Tong Cheng
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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Jun Zhang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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  • For correspondence: zhangj@xmu.edu.cn zhangtianying@xmu.edu.cn zhuhch@hku.hk qinjian_zhao@xmu.edu.cn yuanquan@xmu.edu.cn yguan@hku.hk nsxia@xmu.edu.cn
Tianying Zhang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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  • For correspondence: zhangj@xmu.edu.cn zhangtianying@xmu.edu.cn zhuhch@hku.hk qinjian_zhao@xmu.edu.cn yuanquan@xmu.edu.cn yguan@hku.hk nsxia@xmu.edu.cn
Huachen Zhu
2State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, P. R. China
3Joint Institute of Virology (Shantou University and The University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, P. R. China
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  • For correspondence: zhangj@xmu.edu.cn zhangtianying@xmu.edu.cn zhuhch@hku.hk qinjian_zhao@xmu.edu.cn yuanquan@xmu.edu.cn yguan@hku.hk nsxia@xmu.edu.cn
Qinjian Zhao
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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  • For correspondence: zhangj@xmu.edu.cn zhangtianying@xmu.edu.cn zhuhch@hku.hk qinjian_zhao@xmu.edu.cn yuanquan@xmu.edu.cn yguan@hku.hk nsxia@xmu.edu.cn
Quan Yuan
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
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  • For correspondence: zhangj@xmu.edu.cn zhangtianying@xmu.edu.cn zhuhch@hku.hk qinjian_zhao@xmu.edu.cn yuanquan@xmu.edu.cn yguan@hku.hk nsxia@xmu.edu.cn
Yi Guan
2State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, P. R. China
3Joint Institute of Virology (Shantou University and The University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, P. R. China
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  • For correspondence: zhangj@xmu.edu.cn zhangtianying@xmu.edu.cn zhuhch@hku.hk qinjian_zhao@xmu.edu.cn yuanquan@xmu.edu.cn yguan@hku.hk nsxia@xmu.edu.cn
Ningshao Xia
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen, P. R. China
4Research Unit of Frontier Technology of Structural Vaccinology, Chinese Academy of Medical Sciences, Xiamen 361102, Fujian, China
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  • ORCID record for Ningshao Xia
  • For correspondence: zhangj@xmu.edu.cn zhangtianying@xmu.edu.cn zhuhch@hku.hk qinjian_zhao@xmu.edu.cn yuanquan@xmu.edu.cn yguan@hku.hk nsxia@xmu.edu.cn
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Abstract

A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.

Competing Interest Statement

The authors have declared no competing interest.

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 December 20, 2020.
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Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine
Yangtao Wu, Xiaofen Huang, Lunzhi Yuan, Shaojuan Wang, Yali Zhang, Hualong Xiong, Rirong Chen, Jian Ma, Ruoyao Qi, Meifeng Nie, Jingjing Xu, Zhigang Zhang, Liqiang Chen, Min Wei, Ming Zhou, Minping Cai, Yang Shi, Liang Zhang, Huan Yu, Junping Hong, Zikang Wang, Yunda Hong, Mingxi Yue, Zonglin Li, Dabing Chen, Qingbing Zheng, Shaowei Li, Yixin Chen, Tong Cheng, Jun Zhang, Tianying Zhang, Huachen Zhu, Qinjian Zhao, Quan Yuan, Yi Guan, Ningshao Xia
bioRxiv 2020.12.18.423552; doi: https://doi.org/10.1101/2020.12.18.423552
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Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine
Yangtao Wu, Xiaofen Huang, Lunzhi Yuan, Shaojuan Wang, Yali Zhang, Hualong Xiong, Rirong Chen, Jian Ma, Ruoyao Qi, Meifeng Nie, Jingjing Xu, Zhigang Zhang, Liqiang Chen, Min Wei, Ming Zhou, Minping Cai, Yang Shi, Liang Zhang, Huan Yu, Junping Hong, Zikang Wang, Yunda Hong, Mingxi Yue, Zonglin Li, Dabing Chen, Qingbing Zheng, Shaowei Li, Yixin Chen, Tong Cheng, Jun Zhang, Tianying Zhang, Huachen Zhu, Qinjian Zhao, Quan Yuan, Yi Guan, Ningshao Xia
bioRxiv 2020.12.18.423552; doi: https://doi.org/10.1101/2020.12.18.423552

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