Tags

Type your tag names separated by a space and hit enter

A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS.
Cell. 2020 Jun 28 [Online ahead of print]Cell

Abstract

Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.

Authors+Show Affiliations

Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China; Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine and Laboratory Medicine, The First Affiliated Hospital, Hainan Medical University, Hainan 571199, China. Electronic address: dailp@biols.ac.cn.Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine and Laboratory Medicine, The First Affiliated Hospital, Hainan Medical University, Hainan 571199, China.Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100032, China.Anhui Zhifei Longcom Biopharmaceutical Co. Ltd, Anhui 230088, China.Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.Anhui Zhifei Longcom Biopharmaceutical Co. Ltd, Anhui 230088, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, China.Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; Department of Microbiology-Infectiology and Immunology, Laval University, Quebec City, QC G1V 4G2, Canada.Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100032, China. Electronic address: qinchuan@pumc.edu.cn.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: yanjh@im.ac.cn.Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China. Electronic address: gaof@im.ac.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32645327

Citation

Dai, Lianpan, et al. "A Universal Design of Betacoronavirus Vaccines Against COVID-19, MERS, and SARS." Cell, 2020.
Dai L, Zheng T, Xu K, et al. A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS. Cell. 2020.
Dai, L., Zheng, T., Xu, K., Han, Y., Xu, L., Huang, E., An, Y., Cheng, Y., Li, S., Liu, M., Yang, M., Li, Y., Cheng, H., Yuan, Y., Zhang, W., Ke, C., Wong, G., Qi, J., Qin, C., ... Gao, G. F. (2020). A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS. Cell. https://doi.org/10.1016/j.cell.2020.06.035
Dai L, et al. A Universal Design of Betacoronavirus Vaccines Against COVID-19, MERS, and SARS. Cell. 2020 Jun 28; PubMed PMID: 32645327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS. AU - Dai,Lianpan, AU - Zheng,Tianyi, AU - Xu,Kun, AU - Han,Yuxuan, AU - Xu,Lili, AU - Huang,Enqi, AU - An,Yaling, AU - Cheng,Yingjie, AU - Li,Shihua, AU - Liu,Mei, AU - Yang,Mi, AU - Li,Yan, AU - Cheng,Huijun, AU - Yuan,Yuan, AU - Zhang,Wei, AU - Ke,Changwen, AU - Wong,Gary, AU - Qi,Jianxun, AU - Qin,Chuan, AU - Yan,Jinghua, AU - Gao,George F, Y1 - 2020/06/28/ PY - 2020/05/04/received PY - 2020/06/03/revised PY - 2020/06/23/accepted PY - 2020/7/10/entrez PY - 2020/7/10/pubmed PY - 2020/7/10/medline KW - COVID-19 KW - MERS KW - MERS-CoV KW - SARS KW - SARS-CoV KW - SARS-CoV-2 KW - betacoronavirus KW - coronavirus KW - receptor-binding domain (RBD) KW - vaccine JF - Cell JO - Cell N2 - Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats. SN - 1097-4172 UR - https://www.unboundmedicine.com/medline/citation/32645327/A_Universal_Design_of_Betacoronavirus_Vaccines_against_COVID-19,_MERS,_and_SARS L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(20)30812-6 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.