A single-dose intranasal live-attenuated codon deoptimized vaccine provides broad protection against SARS-CoV-2 and its variants
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.
Authors
- Thomas M. Ashhurst (ORCID: https://orcid.org/0000-0001-7269-7773)
- Joseph R. Freitas (ORCID: https://orcid.org/0000-0003-3104-6282)
- Sridevi V. Nimmagadda
- Sanjay Sarkar (ORCID: https://orcid.org/0000-0003-0933-1415)
- Adam Taylor (ORCID: https://orcid.org/0000-0002-7159-3961)
- Malik Peiris (ORCID: https://orcid.org/0000-0001-8217-5995)
- Samuel M. S. Cheng (ORCID: https://orcid.org/0000-0001-7293-2331)
- Ralph Steven Baric (ORCID: https://orcid.org/0000-0001-6827-8701)
- Mark T. Heise (ORCID: https://orcid.org/0000-0001-5829-8477)
- Nicholas J. C. King (ORCID: https://orcid.org/0000-0002-3877-9772)
- Elizabeth J. Anderson (ORCID: https://orcid.org/0000-0001-7877-1639)
- Rajendra Lingala
- Wern Hann Ng (ORCID: https://orcid.org/0000-0001-8438-7203)
- Eva Žusinaite (ORCID: https://orcid.org/0000-0001-6554-7996)
- Shukra M. Aavula
- Suresh Mahalingam (ORCID: https://orcid.org/0000-0003-3141-8410)
- P. Santhakumar
- Ujjwal Dua
- Andres Merits (ORCID: https://orcid.org/0000-0001-8193-0071)
- Laura Sandra Lello
- Sharon Taft-Benz (ORCID: https://orcid.org/0000-0002-0965-8760)
- Priyabrata Pattnaik (ORCID: https://orcid.org/0000-0002-2314-0052)
- Zheng Lung Ling
- Ali Zaid (ORCID: https://orcid.org/0000-0002-2528-2783)
- Felicity Jane Burt (ORCID: https://orcid.org/0000-0002-7238-7799)
- Victoria K. Baxter (ORCID: https://orcid.org/0000-0003-0916-360X)
- Anand Kumar Kanakasapapathy
- Xiang Liu (ORCID: https://orcid.org/0000-0002-8165-3294)
- Sainan Wang (ORCID: https://orcid.org/0000-0002-7046-4965)
- Rama Lakshmi Bonda
- Venugopal Yerragunta
- Sambaiah Gorriparthi
- Priyanka Mani
Institutions
- National Health Laboratory Service (ZA)
- University of North Carolina at Chapel Hill (US)
- Griffith University (AU)
- The University of Sydney (AU)
- University of the Free State (ZA)
- Centenary Institute (AU)
- Taronga Conservation Society Australia (AU)
- HKU-Pasteur Research Pole (HK)
- Indian Immunologicals (India) (IN)
- University of Tartu (EE)
- University of Hong Kong (HK)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-26
- DOI
- https://doi.org/10.1038/s41467-024-51535-y
- Citations
- 16
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 6.22
Funders
- Griffith University
- National Health and Medical Research Council