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PreprintCited by 20SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections Studiesvaccines and immunoinformatics approaches

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Versatile live attenuated SARS-CoV-2 vaccine platform applicable to variants induces protective immunity

Open access
Yoshida, Akiho, Okamura, Shinya, Torii, Shiho, Komatsu, Sayuri, Miyazato, Paola, Ueno, Shiori, Suzuki, Hidehiko, Kamitani, Wataru, Ono, Chikako, Matsuura, Yoshiharu, Takekawa, Shiro, Yamanishi, Koichi, Ebina, Hirotaka·2021·iScience
DOI 10.1101/2021.02.15.430863PMC PMC9614708

Preprint — published as 10.1016/j.isci.2022.105412 · Paper page

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Abstract

SUMMARY: 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 37-39°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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Metadata

Authors
Yoshida, A., Okamura, S., Torii, S., Komatsu, S., Miyazato, P., 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
openRxiv
Published
2021-02-16
Volume
25
Issue
11
Pages
105412-105412
ISSN
2589-0042 (ISSN-L)
DOI
10.1101/2021.02.15.430863
PMC
PMC9614708
OpenAlex
W4306893972
Cited by
20
References
1
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
Licence
cc-by-nc-nd
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
  • Osaka University
  • BIKEN Foundation
  • Japan Society for the Promotion of Science (22K18378)
  • Collaborative Research Based on Industrial Demand (JP20pc0101047)
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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