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A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions (preprint)
biorxiv; 2022.
Preprint
in English
| bioRxiv | ID: ppzbmed-10.1101.2022.02.14.480460
ABSTRACT
We report a live-attenuated SARS-CoV-2 vaccine candidate with (i) re-engineered viral transcriptional regulator sequences and (ii) deleted open-reading-frames (ORF) 3, 6, 7, and 8 ({triangleup}3678). The {triangleup}3678 virus replicates about 7,500-fold lower than wild-type SARS-CoV-2 on primary human airway cultures, but restores its replication on interferon-deficient Vero-E6 cells that are approved for vaccine production. The {triangleup}3678 virus is highly attenuated in both hamster and K18-hACE2 mouse models. A single-dose immunization of the {triangleup}3678 virus protects hamsters from wild-type virus challenge and transmission. Among the deleted ORFs in the {triangleup}3678 virus, ORF3a accounts for the most attenuation through antagonizing STAT1 phosphorylation during type-I interferon signaling. We also developed an mNeonGreen reporter {triangleup}3678 virus for high-throughput neutralization and antiviral testing. Altogether, the results suggest that {triangleup}3678 SARS-CoV-2 may serve as a live-attenuated vaccine candidate and a research tool for potential biosafety level-2 use.
Full text:
Available
Collection:
Preprints
Database:
bioRxiv
Language:
English
Year:
2022
Document Type:
Preprint
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