Nature Communications (Aug 2024)
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,
- Suresh Mahalingam
Affiliations
- Xiang Liu
- Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University
- Wern Hann Ng
- Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University
- Eva Zusinaite
- Institute of Technology, University of Tartu
- Joseph Freitas
- Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University
- Adam Taylor
- Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University
- Venugopal Yerragunta
- Indian Immunologicals Ltd (IIL), Rakshapuram, Gachibowli Post
- Shukra Madhaha Aavula
- Indian Immunologicals Ltd (IIL), Rakshapuram, Gachibowli Post
- Sambaiah Gorriparthi
- Indian Immunologicals Ltd (IIL), Rakshapuram, Gachibowli Post
- Santhakumar Ponsekaran
- Indian Immunologicals Ltd (IIL), Rakshapuram, Gachibowli Post
- Rama Lakshmi Bonda
- Indian Immunologicals Ltd (IIL), Rakshapuram, Gachibowli Post
- Priyanka Mani
- Indian Immunologicals Ltd (IIL), Rakshapuram, Gachibowli Post
- Sridevi V. Nimmagadda
- Indian Immunologicals Ltd (IIL), Rakshapuram, Gachibowli Post
- Sainan Wang
- Institute of Technology, University of Tartu
- Laura Sandra Lello
- Institute of Technology, University of Tartu
- Ali Zaid
- Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University
- Ujjwal Dua
- Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University
- Sharon A. Taft-Benz
- Department of Genetics, University of North Carolina at Chapel Hill
- Elizabeth Anderson
- Department of Genetics, University of North Carolina at Chapel Hill
- Victoria K. Baxter
- Department of Genetics, University of North Carolina at Chapel Hill
- Sanjay Sarkar
- Department of Genetics, University of North Carolina at Chapel Hill
- Zheng L. Ling
- School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney
- Thomas M. Ashhurst
- School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney
- Samuel M. S. Cheng
- School of Public Health, The University of Hong Kong, Special Administrative Region of Hong Kong
- Priyabrata Pattnaik
- Indian Immunologicals Ltd (IIL), Rakshapuram, Gachibowli Post
- Anand Kumar Kanakasapapathy
- Indian Immunologicals Ltd (IIL), Rakshapuram, Gachibowli Post
- Ralph S. Baric
- Department of Genetics, University of North Carolina at Chapel Hill
- Felicity J. Burt
- Division of Virology, National Health Laboratory Service and Faculty of Health Sciences, University of the Free State
- Malik Peiris
- School of Public Health, The University of Hong Kong, Special Administrative Region of Hong Kong
- Mark T. Heise
- Department of Genetics, University of North Carolina at Chapel Hill
- Nicholas J. C. King
- Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University
- Andres Merits
- Institute of Technology, University of Tartu
- Rajendra Lingala
- Indian Immunologicals Ltd (IIL), Rakshapuram, Gachibowli Post
- Suresh Mahalingam
- Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University
- DOI
- https://doi.org/10.1038/s41467-024-51535-y
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
