SARS-CoV-2 spike produced in insect cells elicits high neutralization titres in non-human primates

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 e...

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Bibliographic Details
Published in:Emerging microbes & infections 2020-01, Vol.9 (1), p.2076-2090
Main Authors: 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
Format: Article
Language:English
Subjects:
Angiotensin-Converting Enzyme 2
Animals
Antibodies, Neutralizing - blood
Antibodies, Neutralizing - immunology
Antibodies, Viral - blood
Antibodies, Viral - immunology
Antigens, Viral - immunology
Betacoronavirus - immunology
Cell Line
Coronavirus Infections - immunology
Coronavirus Infections - prevention & control
Coronaviruses
COVID-19
COVID-19 Vaccines
Cryoelectron Microscopy
Disease transmission
Enzyme-Linked Immunosorbent Assay
Humans
immunogenicity
Immunogenicity, Vaccine - immunology
insect cell expression system
Macaca fascicularis
Mice
Mice, Inbred BALB C
Neutralization Tests
Pandemics - prevention & control
Peptidyl-Dipeptidase A - metabolism
Pneumonia, Viral - prevention & control
Protein Domains - genetics
Protein Domains - immunology
Proteins
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Sf9 Cells
spike
Spike Glycoprotein, Coronavirus - genetics
Spike Glycoprotein, Coronavirus - immunology
Spodoptera
Vaccination
Vaccines
Viral Envelope Proteins - immunology
Viral Vaccines - immunology
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Summary: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.
ISSN:2222-1751
2222-1751
DOI:10.1080/22221751.2020.1821583