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A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS.
Dai, Lianpan; Zheng, Tianyi; Xu, Kun; Han, Yuxuan; Xu, Lili; Huang, Enqi; An, Yaling; Cheng, Yingjie; Li, Shihua; Liu, Mei; Yang, Mi; Li, Yan; Cheng, Huijun; Yuan, Yuan; Zhang, Wei; Ke, Changwen; Wong, Gary; Qi, Jianxun; Qin, Chuan; Yan, Jinghua; Gao, George F.
  • Dai L; 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,
  • Zheng T; 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.
  • Xu K; 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.
  • Han Y; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
  • Xu L; 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.
  • Huang E; Anhui Zhifei Longcom Biopharmaceutical Co. Ltd, Anhui 230088, China.
  • An Y; Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
  • Cheng Y; Anhui Zhifei Longcom Biopharmaceutical Co. Ltd, Anhui 230088, China.
  • Li S; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Liu M; CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Yang M; CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Li Y; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Cheng H; Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
  • Yuan Y; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Zhang W; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Ke C; Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, China.
  • Wong G; 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.
  • Qi J; 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.
  • Qin C; 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.
  • Yan J; 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. Electro
  • Gao GF; 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
Cell ; 182(3): 722-733.e11, 2020 08 06.
Article in English | MEDLINE | ID: covidwho-628738
Semantic information from SemMedBD (by NLM)
1. Vaccines PART_OF Betacoronavirus
Subject
Vaccines
Predicate
PART_OF
Object
Betacoronavirus
2. Vaccines TREATS COVID-19
Subject
Vaccines
Predicate
TREATS
Object
COVID-19
3. Coronavirus Infections CAUSES Severe Acute Respiratory Syndrome
Subject
Coronavirus Infections
Predicate
CAUSES
Object
Severe Acute Respiratory Syndrome
4. Vaccines PART_OF Betacoronavirus
Subject
Vaccines
Predicate
PART_OF
Object
Betacoronavirus
5. Vaccines TREATS COVID-19
Subject
Vaccines
Predicate
TREATS
Object
COVID-19
6. Coronavirus Infections CAUSES Severe Acute Respiratory Syndrome
Subject
Coronavirus Infections
Predicate
CAUSES
Object
Severe Acute Respiratory Syndrome
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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / SARS Virus / Pandemics / Middle East Respiratory Syndrome Coronavirus / Betacoronavirus / Universal Design Type of study: Prognostic study Topics: Vaccines Limits: Animals / Humans Language: English Journal: Cell Year: 2020 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / SARS Virus / Pandemics / Middle East Respiratory Syndrome Coronavirus / Betacoronavirus / Universal Design Type of study: Prognostic study Topics: Vaccines Limits: Animals / Humans Language: English Journal: Cell Year: 2020 Document Type: Article