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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.
    2. Tran Thao & Fabien Labroussaa & Nadine Ebert & Philip V’kovski & Hanspeter Stalder & Jasmine Portmann & Jenna Kelly & Silvio Steiner & Melle Holwerda & Annika Kratzel & Mitra Gultom & Kimberly Schmied, 2020. "Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform," Nature, Nature, vol. 582(7813), pages 561-565, June.
    3. Jessica A. Plante & Yang Liu & Jianying Liu & Hongjie Xia & Bryan A. Johnson & Kumari G. Lokugamage & Xianwen Zhang & Antonio E. Muruato & Jing Zou & Camila R. Fontes-Garfias & Divya Mirchandani & Dio, 2021. "Spike mutation D614G alters SARS-CoV-2 fitness," Nature, Nature, vol. 592(7852), pages 116-121, April.
    4. Mark J. Mulligan & Kirsten E. Lyke & Nicholas Kitchin & Judith Absalon & Alejandra Gurtman & Stephen Lockhart & Kathleen Neuzil & Vanessa Raabe & Ruth Bailey & Kena A. Swanson & Ping Li & Kenneth Kour, 2020. "Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults," Nature, Nature, vol. 586(7830), pages 589-593, October.
    5. Antonio E. Muruato & Camila R. Fontes-Garfias & Ping Ren & Mariano A. Garcia-Blanco & Vineet D. Menachery & Xuping Xie & Pei-Yong Shi, 2020. "A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation," Nature Communications, Nature, vol. 11(1), pages 1-6, December.
    6. Bryan A. Johnson & Xuping Xie & Adam L. Bailey & Birte Kalveram & Kumari G. Lokugamage & Antonio Muruato & Jing Zou & Xianwen Zhang & Terry Juelich & Jennifer K. Smith & Lihong Zhang & Nathen Bopp & C, 2021. "Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis," Nature, Nature, vol. 591(7849), pages 293-299, March.
    7. Jianying Liu & Yang Liu & Hongjie Xia & Jing Zou & Scott C. Weaver & Kena A. Swanson & Hui Cai & Mark Cutler & David Cooper & Alexander Muik & Kathrin U. Jansen & Ugur Sahin & Xuping Xie & Philip R. D, 2021. "BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants," Nature, Nature, vol. 596(7871), pages 273-275, August.
    8. Xuping Xie & Antonio E. Muruato & Xianwen Zhang & Kumari G. Lokugamage & Camila R. Fontes-Garfias & Jing Zou & Jianying Liu & Ping Ren & Mini Balakrishnan & Tomas Cihlar & Chien-Te K. Tseng & Shinji M, 2020. "A nanoluciferase SARS-CoV-2 for rapid neutralization testing and screening of anti-infective drugs for COVID-19," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    9. Zhiqiang Ku & Xuping Xie & Paul R. Hinton & Xinli Liu & Xiaohua Ye & Antonio E. Muruato & Dean C. Ng & Sujit Biswas & Jing Zou & Yang Liu & Deepal Pandya & Vineet D. Menachery & Sachi Rahman & Yu-An C, 2021. "Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants," Nature, Nature, vol. 595(7869), pages 718-723, July.
    10. Jessica A. Plante & Yang Liu & Jianying Liu & Hongjie Xia & Bryan A. Johnson & Kumari G. Lokugamage & Xianwen Zhang & Antonio E. Muruato & Jing Zou & Camila R. Fontes-Garfias & Divya Mirchandani & Dio, 2021. "Author Correction: Spike mutation D614G alters SARS-CoV-2 fitness," Nature, Nature, vol. 595(7865), pages 1-1, July.
    11. 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. "Molecular determinants and mechanism for antibody cocktail preventing SARS-CoV-2 escape," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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    1. 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.
    2. 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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