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

Author

Listed:
  • Yang Liu

    (University of Texas Medical Branch)

  • Xianwen Zhang

    (University of Texas Medical Branch)

  • Jianying Liu

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Hongjie Xia

    (University of Texas Medical Branch)

  • Jing Zou

    (University of Texas Medical Branch)

  • Antonio E. Muruato

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Sivakumar Periasamy

    (University of Texas Medical Branch
    Galveston National Laboratory)

  • Chaitanya Kurhade

    (University of Texas Medical Branch)

  • Jessica A. Plante

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

  • Nathen E. Bopp

    (University of Texas Medical Branch)

  • Birte Kalveram

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Alexander Bukreyev

    (University of Texas Medical Branch
    University of Texas Medical Branch
    Galveston National Laboratory)

  • Ping Ren

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Tian Wang

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

  • Vineet D. Menachery

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Kenneth S. Plante

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

  • Xuping Xie

    (University of Texas Medical Branch)

  • Scott C. Weaver

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

  • Pei-Yong Shi

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

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.

Suggested Citation

  • Yang Liu & Xianwen Zhang & Jianying Liu & Hongjie Xia & Jing Zou & Antonio E. Muruato & Sivakumar Periasamy & Chaitanya Kurhade & Jessica A. Plante & Nathen E. Bopp & Birte Kalveram & Alexander Bukrey, 2022. "A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31930-z
    DOI: 10.1038/s41467-022-31930-z
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    as
    1. Zhiqiang Ku & Xuping Xie & Edgar Davidson & Xiaohua Ye & Hang Su & Vineet D. Menachery & Yize Li & Zihao Yuan & Xianwen Zhang & Antonio E. Muruato & Ariadna Grinyo i Escuer & Breanna Tyrell & Kyle Doo, 2021. "Author Correction: Molecular determinants and mechanism for antibody cocktail preventing SARS-CoV-2 escape," Nature Communications, Nature, vol. 12(1), pages 1-1, December.
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    2. Taha Y. Taha & Irene P. Chen & Jennifer M. Hayashi & Takako Tabata & Keith Walcott & Gabriella R. Kimmerly & Abdullah M. Syed & Alison Ciling & Rahul K. Suryawanshi & Hannah S. Martin & Bryan H. Bach , 2023. "Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Bruno A. Rodriguez-Rodriguez & Grace O. Ciabattoni & Ralf Duerr & Ana M. Valero-Jimenez & Stephen T. Yeung & Keaton M. Crosse & Austin R. Schinlever & Lucie Bernard-Raichon & Joaquin Rodriguez Galvan , 2023. "A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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