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A single-dose intranasal live-attenuated codon deoptimized vaccine provides broad protection against SARS-CoV-2 and its variants

Author

Listed:
  • Xiang Liu

    (Griffith University
    Griffith University
    Griffith University)

  • Wern Hann Ng

    (Griffith University
    Griffith University
    Griffith University)

  • Eva Zusinaite

    (University of Tartu)

  • Joseph Freitas

    (Griffith University
    Griffith University
    Griffith University)

  • Adam Taylor

    (Griffith University
    Griffith University
    Griffith University)

  • Venugopal Yerragunta

    (Gachibowli Post)

  • Shukra Madhaha Aavula

    (Gachibowli Post)

  • Sambaiah Gorriparthi

    (Gachibowli Post)

  • Santhakumar Ponsekaran

    (Gachibowli Post)

  • Rama Lakshmi Bonda

    (Gachibowli Post)

  • Priyanka Mani

    (Gachibowli Post)

  • Sridevi V. Nimmagadda

    (Gachibowli Post)

  • Sainan Wang

    (University of Tartu)

  • Laura Sandra Lello

    (University of Tartu)

  • Ali Zaid

    (Griffith University
    Griffith University
    Griffith University)

  • Ujjwal Dua

    (Griffith University
    Griffith University)

  • Sharon A. Taft-Benz

    (University of North Carolina at Chapel Hill)

  • Elizabeth Anderson

    (University of North Carolina at Chapel Hill)

  • Victoria K. Baxter

    (University of North Carolina at Chapel Hill)

  • Sanjay Sarkar

    (University of North Carolina at Chapel Hill)

  • Zheng L. Ling

    (The University of Sydney)

  • Thomas M. Ashhurst

    (The University of Sydney
    The University of Sydney and Centenary Institute)

  • Samuel M. S. Cheng

    (Special Administrative Region of Hong Kong)

  • Priyabrata Pattnaik

    (Gachibowli Post)

  • Anand Kumar Kanakasapapathy

    (Gachibowli Post)

  • Ralph S. Baric

    (University of North Carolina at Chapel Hill)

  • Felicity J. Burt

    (University of the Free State)

  • Malik Peiris

    (Special Administrative Region of Hong Kong
    Special Administrative Region of Hong Kong)

  • Mark T. Heise

    (University of North Carolina at Chapel Hill)

  • Nicholas J. C. King

    (Griffith University
    The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Andres Merits

    (University of Tartu)

  • Rajendra Lingala

    (Gachibowli Post)

  • Suresh Mahalingam

    (Griffith University
    Griffith University
    Griffith University)

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) continues its significant health and economic impact globally. Despite the success of spike-protein vaccines in preventing severe disease, long-lasting protection against emerging variants and the prevention of breakthrough infections and transmission remain elusive. We generate an intranasal live-attenuated SARS-CoV-2 vaccine, CDO-7N-1, using codon deoptimization. CDO-7N-1 shows highly attenuated replication and minimal or no lung pathology in vivo over multiple passages. It induces robust mucosal and systemic neutralizing antibody and T-cell subset responses, in mice (female K18-hACE2 and male HFH4-hACE2 mice), hamsters, and macaques triggered by a single immunization. Mice and hamsters vaccinated with CDO-7N-1 are protected from challenge with wild-type (WT) SARS-CoV-2 and other variants of concern. Serum from vaccinated animals neutralizes WT SARS-CoV-2, variants of concern (beta and delta), variants of interest (omicron XBB.1.5) and SARS-CoV-1. Antibody responses are sustained and enhanced by repeated immunization or infection with WT SARS-CoV-2. Immunity against all SARS-CoV-2 proteins by CDO-7N-1 should improve efficacy against future SARS-CoV-2 variants.

Suggested Citation

  • Xiang Liu & Wern Hann Ng & Eva Zusinaite & Joseph Freitas & Adam Taylor & Venugopal Yerragunta & Shukra Madhaha Aavula & Sambaiah Gorriparthi & Santhakumar Ponsekaran & Rama Lakshmi Bonda & Priyanka M, 2024. "A single-dose intranasal live-attenuated codon deoptimized vaccine provides broad protection against SARS-CoV-2 and its variants," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51535-y
    DOI: 10.1038/s41467-024-51535-y
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    References listed on IDEAS

    as
    1. 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.
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