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A single-dose intranasal live-attenuated codon deoptimized vaccine provides broad protection against SARS-CoV-2 and its variants.
- Source :
-
Nature communications [Nat Commun] 2024 Aug 26; Vol. 15 (1), pp. 7225. Date of Electronic Publication: 2024 Aug 26. - Publication Year :
- 2024
-
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.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Female
Male
Humans
Cricetinae
Codon
Spike Glycoprotein, Coronavirus immunology
Spike Glycoprotein, Coronavirus genetics
T-Lymphocytes immunology
Chlorocebus aethiops
COVID-19 Vaccines immunology
COVID-19 Vaccines administration & dosage
SARS-CoV-2 immunology
SARS-CoV-2 genetics
Administration, Intranasal
COVID-19 prevention & control
COVID-19 immunology
COVID-19 virology
Vaccines, Attenuated immunology
Vaccines, Attenuated administration & dosage
Vaccines, Attenuated genetics
Antibodies, Neutralizing immunology
Antibodies, Viral immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39187479
- Full Text :
- https://doi.org/10.1038/s41467-024-51535-y