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Rapid development of SARS-CoV-2 receptor binding domain-conjugated nanoparticle vaccine candidate

Yin-Feng Kang, Cong Sun, Zhen Zhuang, Run-Yu Yuan, Qing-Bing Zheng, Jiang-Ping Li, Ping-Ping Zhou, Xin-Chun Chen, Xiao Zhang, Xiao-Hui Yu, Xiang-Wei Kong, Qian-Ying Zhu, Miao Xu, Nan-Shan Zhong, Yi-Xin Zeng, Guo-Kai Feng, Chang-Wen Ke, Jin-Cun Zhao, Mu-Sheng Zeng
doi: https://doi.org/10.1101/2020.11.03.366138
Yin-Feng Kang
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Cong Sun
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Zhen Zhuang
2State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China
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Run-Yu Yuan
3Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, Guangdong, P. R. China
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Qing-Bing Zheng
4State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, Fujian, PR China
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Jiang-Ping Li
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Ping-Ping Zhou
3Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, Guangdong, P. R. China
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Xin-Chun Chen
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Xiao Zhang
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Xiao-Hui Yu
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Xiang-Wei Kong
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Qian-Ying Zhu
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Miao Xu
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Nan-Shan Zhong
2State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China
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Yi-Xin Zeng
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Guo-Kai Feng
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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  • For correspondence: fengguok@sysucc.org.cn kecw1965@aliyun.com zhaojincun@gird.cn zengmsh@sysucc.org.cn
Chang-Wen Ke
3Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, Guangdong, P. R. China
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  • For correspondence: fengguok@sysucc.org.cn kecw1965@aliyun.com zhaojincun@gird.cn zengmsh@sysucc.org.cn
Jin-Cun Zhao
2State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China
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  • For correspondence: fengguok@sysucc.org.cn kecw1965@aliyun.com zhaojincun@gird.cn zengmsh@sysucc.org.cn
Mu-Sheng Zeng
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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  • For correspondence: fengguok@sysucc.org.cn kecw1965@aliyun.com zhaojincun@gird.cn zengmsh@sysucc.org.cn
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Abstract

The ongoing of coronavirus disease 2019 (COVID-19) pandemic caused by novel SARS-CoV-2 coronavirus, resulting in economic losses and seriously threating the human health in worldwide, highlighting the urgent need of a stabilized, easily produced and effective preventive vaccine. The SARS-COV-2 spike protein receptor binding region (RBD) plays an important role in the process of viral binding receptor angiotensin-converting enzyme 2 (ACE2) and membrane fusion, making it an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticles vaccine candidates, RBD-Ferritin (24-mer), RBD-mi3 (60-mer) and RBD-I53-50 (120-mer), with the application of covalent bond linking by SpyTag-SpyCatcher system. It was demonstrated that the neutralizing capability of sera from mice immunized with three RBD-conjugated nanoparticles adjuvanted with AddaVax or Sigma Systerm Adjuvant (SAS) after each immunization was ~8-to 120-fold greater than monomeric RBD group in SARS-CoV-2 pseudovirus and authentic virus neutralization assay. Most importantly, sera from RBD-conjugated NPs groups more efficiently blocked the binding of RBD to ACE2 or neutralizing antibody in vitro, a further proof of promising immunization effect. Besides, high physical stability and flexibility in assembly consolidated the benefit for rapid scale-up production of vaccine. These results supported that our designed SARS-CoV-2 RBD-conjugated nanoparticle was competitive vaccine candidate and the carrier nanoparticles could be adopted as universal platform for future vaccine development.

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 November 03, 2020.
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Rapid development of SARS-CoV-2 receptor binding domain-conjugated nanoparticle vaccine candidate
Yin-Feng Kang, Cong Sun, Zhen Zhuang, Run-Yu Yuan, Qing-Bing Zheng, Jiang-Ping Li, Ping-Ping Zhou, Xin-Chun Chen, Xiao Zhang, Xiao-Hui Yu, Xiang-Wei Kong, Qian-Ying Zhu, Miao Xu, Nan-Shan Zhong, Yi-Xin Zeng, Guo-Kai Feng, Chang-Wen Ke, Jin-Cun Zhao, Mu-Sheng Zeng
bioRxiv 2020.11.03.366138; doi: https://doi.org/10.1101/2020.11.03.366138
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Rapid development of SARS-CoV-2 receptor binding domain-conjugated nanoparticle vaccine candidate
Yin-Feng Kang, Cong Sun, Zhen Zhuang, Run-Yu Yuan, Qing-Bing Zheng, Jiang-Ping Li, Ping-Ping Zhou, Xin-Chun Chen, Xiao Zhang, Xiao-Hui Yu, Xiang-Wei Kong, Qian-Ying Zhu, Miao Xu, Nan-Shan Zhong, Yi-Xin Zeng, Guo-Kai Feng, Chang-Wen Ke, Jin-Cun Zhao, Mu-Sheng Zeng
bioRxiv 2020.11.03.366138; doi: https://doi.org/10.1101/2020.11.03.366138

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