SARS-CoV-2 spike produced in insect cells elicits high neutralization titres in non-human primates.
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 (1â
µg) with the inclusion of an aluminium adjuvant. Higher doses (20â
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.
Keywords
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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