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A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions.
Liu, Yang; Zhang, Xianwen; Liu, Jianying; Xia, Hongjie; Zou, Jing; Muruato, Antonio E; Periasamy, Sivakumar; Kurhade, Chaitanya; Plante, Jessica A; Bopp, Nathen E; Kalveram, Birte; Bukreyev, Alexander; Ren, Ping; Wang, Tian; Menachery, Vineet D; Plante, Kenneth S; Xie, Xuping; Weaver, Scott C; Shi, Pei-Yong.
Afiliação
  • 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.
  • Xia H; Institute for Human Infections and Immunity, 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.
  • Periasamy S; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
  • Kurhade C; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
  • Plante JA; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
  • Bopp NE; Galveston National Laboratory, Galveston, TX, USA.
  • Kalveram B; 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.
  • Ren P; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
  • Wang T; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.
  • Menachery VD; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
  • Plante KS; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
  • Xie X; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
  • Weaver SC; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
  • Shi PY; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
Nat Commun ; 13(1): 4337, 2022 07 27.
Article em En | MEDLINE | ID: mdl-35896528
ABSTRACT
We report a live-attenuated SARS-CoV-2 vaccine candidate with (i) re-engineered viral transcription regulator sequences and (ii) deleted open-reading-frames (ORF) 3, 6, 7, and 8 (∆3678). The ∆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 ∆3678 virus is highly attenuated in both hamster and K18-hACE2 mouse models. A single-dose immunization of the ∆3678 virus protects hamsters from wild-type virus challenge and transmission. Among the deleted ORFs in the ∆3678 virus, ORF3a accounts for the most attenuation through antagonizing STAT1 phosphorylation during type-I interferon signaling. We also developed an mNeonGreen reporter ∆3678 virus for high-throughput neutralization and antiviral testing. Altogether, the results suggest that ∆3678 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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacinas contra COVID-19 / COVID-19 Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacinas contra COVID-19 / COVID-19 Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos