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SARS-CoV-2 spike produced in insect cells elicits high neutralization titres in non-human primates.
Li, Tingting; Zheng, Qingbing; Yu, Hai; Wu, Dinghui; Xue, Wenhui; Xiong, Hualong; Huang, Xiaofen; Nie, Meifeng; Yue, Mingxi; Rong, Rui; Zhang, Sibo; Zhang, Yuyun; Wu, Yangtao; Wang, Shaojuan; Zha, Zhenghui; Chen, Tingting; Deng, Tingting; Wang, Yingbin; Zhang, Tianying; Chen, Yixin; Yuan, Quan; Zhao, Qinjian; Zhang, Jun; Gu, Ying; Li, Shaowei; Xia, Ningshao.
  • Li T; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, People's Republic of China.
  • Zheng Q; National Institute of Diagnostics and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, People's Republic of China.
  • Yu H; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, People's Republic of China.
  • Wu D; National Institute of Diagnostics and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, People's Republic of China.
  • Xue W; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, People's Republic of China.
  • Xiong H; National Institute of Diagnostics and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, People's Republic of China.
  • Huang X; Department of Pulmonary Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
  • Nie M; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, People's Republic of China.
  • Yue M; National Institute of Diagnostics and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, People's Republic of China.
  • Rong R; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, People's Republic of China.
  • Zhang S; National Institute of Diagnostics and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, People's Republic of China.
  • Zhang Y; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, People's Republic of China.
  • Wu Y; National Institute of Diagnostics and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, People's Republic of China.
  • Wang S; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, People's Republic of China.
  • Zha Z; National Institute of Diagnostics and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, People's Republic of China.
  • Chen T; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, People's Republic of China.
  • Deng T; National Institute of Diagnostics and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, People's Republic of China.
  • Wang Y; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, People's Republic of China.
  • Zhang T; National Institute of Diagnostics and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, People's Republic of China.
  • Chen Y; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, People's Republic of China.
  • Yuan Q; National Institute of Diagnostics and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, People's Republic of China.
  • Zhao Q; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, People's Republic of China.
  • Zhang J; National Institute of Diagnostics and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, People's Republic of China.
  • Gu Y; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, People's Republic of China.
  • Li S; National Institute of Diagnostics and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, People's Republic of China.
  • Xia N; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, People's Republic of China.
Emerg Microbes Infect ; 9(1): 2076-2090, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-913103
ABSTRACT
The current coronavirus disease 2019 (COVID-19) pandemic was the result of the rapid transmission of a highly pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is no efficacious vaccine or therapeutic. Toward the development of a vaccine, here we expressed and evaluated as potential candidates four versions of the spike (S) protein using an insect cell expression system receptor binding domain (RBD), S1 subunit, the wild-type S ectodomain (S-WT), and the prefusion trimer-stabilized form (S-2P). We showed that RBD appears as a monomer in solution, whereas S1, S-WT, and S-2P associate as homotrimers with substantial glycosylation. Cryo-electron microscopy analyses suggested that S-2P assumes an identical trimer conformation as the similarly engineered S protein expressed in 293 mammalian cells but with reduced glycosylation. Overall, the four proteins confer excellent antigenicity with convalescent COVID-19 patient sera in enzyme-linked immunosorbent assay (ELISA), yet show distinct reactivities in immunoblotting. RBD, S-WT and S-2P, but not S1, induce high neutralization titres (>3-log) in mice after a three-round immunization regimen. The high immunogenicity of S-2P could be maintained at the lowest dose (1 µg) with the inclusion of an aluminium adjuvant. Higher doses (20 µg) of S-2P can elicit high neutralization titres in non-human primates that exceed 40-times the mean titres measured in convalescent COVID-19 subjects. Our results suggest that the prefusion trimer-stabilized SARS-CoV-2 S-protein from insect cells may offer a potential candidate strategy for the development of a recombinant COVID-19 vaccine.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Viral Vaccines / Coronavirus Infections / Pandemics / Spike Glycoprotein, Coronavirus / Immunogenicity, Vaccine / Betacoronavirus / Antigens, Viral Type of study: Experimental Studies Topics: Vaccines Limits: Animals / Humans Language: English Journal: Emerg Microbes Infect Year: 2020 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Viral Vaccines / Coronavirus Infections / Pandemics / Spike Glycoprotein, Coronavirus / Immunogenicity, Vaccine / Betacoronavirus / Antigens, Viral Type of study: Experimental Studies Topics: Vaccines Limits: Animals / Humans Language: English Journal: Emerg Microbes Infect Year: 2020 Document Type: Article