SARS-CoV-2 virus lacking the envelope and membrane open-reading frames as a vaccine platform
Abstract To address the need for broadly protective SARS-CoV-2 vaccines, we developed an attenuated a SARS-CoV-2 vaccine virus that lacks the open reading frames of two viral structural proteins: the envelope (E) and membrane (M) proteins. This vaccine virus (ΔEM) replicates in a cell line stably ex...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59533-4 |
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| author | Makoto Kuroda Peter J. Halfmann Ryuta Uraki Seiya Yamayoshi Taksoo Kim Tammy A. Armbrust Sam Spyra Randall Dahn Lavanya Babujee Yoshihiro Kawaoka |
| author_facet | Makoto Kuroda Peter J. Halfmann Ryuta Uraki Seiya Yamayoshi Taksoo Kim Tammy A. Armbrust Sam Spyra Randall Dahn Lavanya Babujee Yoshihiro Kawaoka |
| author_sort | Makoto Kuroda |
| collection | DOAJ |
| description | Abstract To address the need for broadly protective SARS-CoV-2 vaccines, we developed an attenuated a SARS-CoV-2 vaccine virus that lacks the open reading frames of two viral structural proteins: the envelope (E) and membrane (M) proteins. This vaccine virus (ΔEM) replicates in a cell line stably expressing E and M but not in wild-type cells. Vaccination with ΔEM elicits a CD8 T-cell response against the viral spike and nucleocapsid proteins. Two vaccinations with ΔEM provide better protection of the lower respiratory tissues than a single dose against the Delta and Omicron XBB variants in hamsters. Moreover, ΔEM is effective as a booster in hamsters previously vaccinated with an mRNA-based vaccine, providing higher levels of protection in both respiratory tissues compared to the mRNA vaccine booster. Collectively, our data demonstrate the feasibility of a SARS-CoV-2 ΔEM vaccine candidate virus as a vaccine platform. |
| format | Article |
| id | doaj-art-718a470de9174d0b9afc4e90ed760dd3 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-718a470de9174d0b9afc4e90ed760dd32025-08-20T01:51:30ZengNature PortfolioNature Communications2041-17232025-05-0116111410.1038/s41467-025-59533-4SARS-CoV-2 virus lacking the envelope and membrane open-reading frames as a vaccine platformMakoto Kuroda0Peter J. Halfmann1Ryuta Uraki2Seiya Yamayoshi3Taksoo Kim4Tammy A. Armbrust5Sam Spyra6Randall Dahn7Lavanya Babujee8Yoshihiro Kawaoka9Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of WisconsinInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of WisconsinDivision of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of TokyoDivision of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of TokyoInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of WisconsinInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of WisconsinInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of WisconsinInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of WisconsinInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of WisconsinInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of WisconsinAbstract To address the need for broadly protective SARS-CoV-2 vaccines, we developed an attenuated a SARS-CoV-2 vaccine virus that lacks the open reading frames of two viral structural proteins: the envelope (E) and membrane (M) proteins. This vaccine virus (ΔEM) replicates in a cell line stably expressing E and M but not in wild-type cells. Vaccination with ΔEM elicits a CD8 T-cell response against the viral spike and nucleocapsid proteins. Two vaccinations with ΔEM provide better protection of the lower respiratory tissues than a single dose against the Delta and Omicron XBB variants in hamsters. Moreover, ΔEM is effective as a booster in hamsters previously vaccinated with an mRNA-based vaccine, providing higher levels of protection in both respiratory tissues compared to the mRNA vaccine booster. Collectively, our data demonstrate the feasibility of a SARS-CoV-2 ΔEM vaccine candidate virus as a vaccine platform.https://doi.org/10.1038/s41467-025-59533-4 |
| spellingShingle | Makoto Kuroda Peter J. Halfmann Ryuta Uraki Seiya Yamayoshi Taksoo Kim Tammy A. Armbrust Sam Spyra Randall Dahn Lavanya Babujee Yoshihiro Kawaoka SARS-CoV-2 virus lacking the envelope and membrane open-reading frames as a vaccine platform Nature Communications |
| title | SARS-CoV-2 virus lacking the envelope and membrane open-reading frames as a vaccine platform |
| title_full | SARS-CoV-2 virus lacking the envelope and membrane open-reading frames as a vaccine platform |
| title_fullStr | SARS-CoV-2 virus lacking the envelope and membrane open-reading frames as a vaccine platform |
| title_full_unstemmed | SARS-CoV-2 virus lacking the envelope and membrane open-reading frames as a vaccine platform |
| title_short | SARS-CoV-2 virus lacking the envelope and membrane open-reading frames as a vaccine platform |
| title_sort | sars cov 2 virus lacking the envelope and membrane open reading frames as a vaccine platform |
| url | https://doi.org/10.1038/s41467-025-59533-4 |
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