A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions.

Autor: Liu Y; Department of Biochemistry and Molecular Biology,University of Texas Medical Branch, Galveston TX, USA., Zhang X; Department of Biochemistry and Molecular Biology,University of Texas Medical Branch, Galveston TX, USA., Liu J; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, USA.; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA., Xia H; Department of Biochemistry and Molecular Biology,University of Texas Medical Branch, Galveston TX, USA., Zou J; Department of Biochemistry and Molecular Biology,University of Texas Medical Branch, Galveston TX, USA., Muruato AE; Department of Biochemistry and Molecular Biology,University of Texas Medical Branch, Galveston TX, USA.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, USA.; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA., Periasamy S; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.; Galveston National Laboratory, Galveston, Texas, USA., Plante JA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, USA.; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA., Bopp NE; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA., Kurhade C; Department of Biochemistry and Molecular Biology,University of Texas Medical Branch, Galveston TX, USA., Bukreyev A; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, USA.; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.; Galveston National Laboratory, Galveston, Texas, USA., Ren P; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA., Wang T; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, USA.; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.; Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, USA., Menachery VD; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, USA.; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA., Plante KS; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, USA.; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA., Xie X; Department of Biochemistry and Molecular Biology,University of Texas Medical Branch, Galveston TX, USA., Weaver SC; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, USA.; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.; Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, USA., Shi PY; Department of Biochemistry and Molecular Biology,University of Texas Medical Branch, Galveston TX, USA.; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.; Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, USA.; Sealy Institute for Drug Discovery, University of Texas Medical Branch, Galveston, TX, USA.; Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2022 Feb 15. Date of Electronic Publication: 2022 Feb 15.
DOI: 10.1101/2022.02.14.480460
Abstrakt: 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.
Databáze: MEDLINE