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

Xiang Liu, Wern Hann Ng, Eva Zusinaite, Joseph Freitas, Adam Taylor, Venugopal Yerragunta, Shukra Madhaha Aavula, Sambaiah Gorriparthi, Santhakumar Ponsekaran, Rama Lakshmi Bonda, Priyanka Mani, Sridevi V. Nimmagadda, Sainan Wang, Laura Sandra Lello, Ali Zaid, Ujjwal Dua, Sharon A. Taft-Benz, Elizabeth Anderson, Victoria K. Baxter, Sanjay Sarkar, Zheng L. Ling, Thomas M. Ashhurst, Samuel M. S. Cheng, Priyabrata Pattnaik, Anand Kumar Kanakasapapathy, Ralph S. Baric, Felicity J. Burt, Malik Peiris, Mark T. Heise, Nicholas J. C. King, Andres Merits, Rajendra Lingala and Suresh Mahalingam ()
Additional contact information
Xiang Liu: Griffith University
Wern Hann Ng: Griffith University
Eva Zusinaite: University of Tartu
Joseph Freitas: Griffith University
Adam Taylor: 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
Ujjwal Dua: 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
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
Mark T. Heise: University of North Carolina at Chapel Hill
Nicholas J. C. King: Griffith University
Andres Merits: University of Tartu
Rajendra Lingala: Gachibowli Post
Suresh Mahalingam: Griffith University

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-51535-y

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