Versatile live-attenuated SARS-CoV-2 vaccine platform applicable to variants induces protective immunity
Open accessPublished version of a preprint
Abstract
Live-attenuated vaccines are generally highly effective. Here, we aimed to develop one against SARS-CoV-2, based on the identification of three types of temperature-sensitive (TS) strains with mutations in nonstructural proteins (nsp), impaired proliferation at 37°C–39°C, and the capacity to induce protective immunity in Syrian hamsters. To develop a live-attenuated vaccine, we generated a virus that combined all these TS-associated mutations (rTS-all), which showed a robust TS phenotype in vitro and high attenuation in vivo . The vaccine induced an effective cross-reactive immune response and protected hamsters against homologous or heterologous viral challenges. Importantly, rTS-all rarely reverted to the wild-type phenotype. By combining these mutations with an Omicron spike protein to construct a recombinant virus, protection against the Omicron strain was obtained. We show that immediate and effective live-attenuated vaccine candidates against SARS-CoV-2 variants may be developed using rTS-all as a backbone to incorporate the spike protein of the variants.
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- Authors
- Yoshida, A., Okamura, S., Torii, S., Komatsu, S., Miyazato, P., Sasaki, H., Ueno, S., Suzuki, H., Kamitani, W., Ono, C., Matsuura, Y., Takekawa, S., Yamanishi, K., & Ebina, H.
- Affiliations
- BIKEN Foundation (JP)
- Center for Infectious Disease Education and Research, The University of Osaka (JP)
- Gunma University (JP)
- Corresponding author
- Ebina, Hirotaka
- ORCID
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2022-11
- Volume
- 25
- Issue
- 11
- Pages
- 105412
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC9614708
- OpenAlex
- W4306893972
- Cited by
- 20
- References
- 8
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 2 · 2021: 2
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Agency for Medical Research and Development Department of Industrial Academic Collaboration (JP20pc0101047)
- BIKEN Foundation
- Japan Agency for Medical Research and Development
- Osaka University
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- live attenuated vaccine, SARS-CoV-2, temperature-sensitive mutation, non-structural proteins, immunological cross-reactivity, heterologous challenge protection, Syrian hamster model, vaccine attenuation, SARS-CoV-2 variants
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