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

doi:10.1038/s41467-024-51535-y

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

Nat Commun. 2024 Aug 26;15(1):7225. doi: 10.1038/s41467-024-51535-y.

Authors

Xiang Liu^{1

2

3}, Wern Hann Ng^{1

2

3}, Eva Zusinaite⁴, Joseph Freitas^{1

2

3}, Adam Taylor^{1

2

3}, Venugopal Yerragunta⁵, Shukra Madhaha Aavula⁵, Sambaiah Gorriparthi⁵, Santhakumar Ponsekaran⁵, Rama Lakshmi Bonda⁵, Priyanka Mani⁵, Sridevi V Nimmagadda⁵, Sainan Wang⁴, Laura Sandra Lello⁴, Ali Zaid^{1

2

3}, Ujjwal Dua^{1

6}, Sharon A Taft-Benz⁷, Elizabeth Anderson⁷, Victoria K Baxter⁷, Sanjay Sarkar⁷, Zheng L Ling⁸, Thomas M Ashhurst^{8

9}, Samuel M S Cheng¹⁰, Priyabrata Pattnaik⁵, Anand Kumar Kanakasapapathy⁵, Ralph S Baric⁷, Felicity J Burt¹¹, Malik Peiris^{10

12}, Mark T Heise⁷, Nicholas J C King^{1

8

13

14

15}, Andres Merits⁴, Rajendra Lingala⁵, Suresh Mahalingam^{16

17

18}

Affiliations

¹ Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia.
² Global Virus Network (GVN) Centre of Excellence in Arboviruses, Griffith University, Gold Coast, QLD, Australia.
³ School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD, Australia.
⁴ Institute of Technology, University of Tartu, 50411, Tartu, Estonia.
⁵ Indian Immunologicals Ltd (IIL), Rakshapuram, Gachibowli Post, Hyderabad, 500032, Telangana, India.
⁶ Griffith Enterprise, Griffith University, Brisbane, QLD, Australia.
⁷ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁸ School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
⁹ Sydney Cytometry Core Research Facility, The University of Sydney and Centenary Institute, Sydney, NSW, Australia.
¹⁰ School of Public Health, The University of Hong Kong, Special Administrative Region of Hong Kong, Hong Kong, China.
¹¹ Division of Virology, National Health Laboratory Service and Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.
¹² HKU-Pasteur Research Pole, The University of Hong Kong, Special Administrative Region of Hong Kong, Hong Kong, China.
¹³ Viral Immunopathology Laboratory, The Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia.
¹⁴ Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW 2006, Australia.
¹⁵ Sydney Nano, The University of Sydney, Sydney, NSW 2006, Australia.
¹⁶ Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia. [email protected].
¹⁷ Global Virus Network (GVN) Centre of Excellence in Arboviruses, Griffith University, Gold Coast, QLD, Australia. [email protected].
¹⁸ School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD, Australia. [email protected].

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.

MeSH terms

Administration, Intranasal*
Animals
Antibodies, Neutralizing* / immunology
Antibodies, Viral* / immunology
COVID-19 Vaccines* / administration & dosage
COVID-19 Vaccines* / immunology
COVID-19* / immunology
COVID-19* / prevention & control
COVID-19* / virology
Chlorocebus aethiops
Codon
Cricetinae
Female
Humans
Male
Mice
SARS-CoV-2* / genetics
SARS-CoV-2* / immunology
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / immunology
T-Lymphocytes / immunology
Vaccines, Attenuated* / administration & dosage
Vaccines, Attenuated* / genetics
Vaccines, Attenuated* / immunology

Substances

COVID-19 Vaccines
Vaccines, Attenuated
Antibodies, Neutralizing
Antibodies, Viral
Codon
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Supplementary concepts

SARS-CoV-2 variants

Abstract

MeSH terms

Substances

Supplementary concepts

Grants and funding