ArticlebioRxiv : the preprint server for biology2022
A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions.
Article in bioRxiv : the preprint server for biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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0 citing papers in PubMed, 9 citations in OpenAlex.
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
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 (Δ3678). The Δ3678 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 Δ3678 virus is highly attenuated in both hamster and K18-hACE2 mouse models. A single-dose immunization of the Δ3678 virus protects hamsters from wild-type virus challenge and transmission. Among the deleted ORFs in the Δ3678 virus, ORF3a accounts for the most attenuation through antagonizing STAT1 phosphorylation during type-I interferon signaling. We also developed an mNeonGreen reporter Δ3678 virus for high-throughput neutralization and antiviral testing. Altogether, the results suggest that Δ3678 SARS-CoV-2 may serve as a live-attenuated vaccine candidate and a research tool for potential biosafety level-2 use.
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