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A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions
We report a live-attenuated SARS-CoV-2 vaccine candidate with (i) re-engineered viral transcription regulator sequences and (ii) deleted open-reading-frames (ORF) 3, 6, 7, and 8 (∆3678). The ∆3678 virus replicates about 7,500-fold lower than wild-type SARS-CoV-2 on primary human airway cultures, but...
| Autores principales: | , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2022
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326133/ https://www.ncbi.nlm.nih.gov/pubmed/35896528 http://dx.doi.org/10.1038/s41467-022-31930-z |
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| author | Liu, Yang Zhang, Xianwen Liu, Jianying Xia, Hongjie Zou, Jing Muruato, Antonio E. Periasamy, Sivakumar Kurhade, Chaitanya Plante, Jessica A. Bopp, Nathen E. Kalveram, Birte Bukreyev, Alexander Ren, Ping Wang, Tian Menachery, Vineet D. Plante, Kenneth S. Xie, Xuping Weaver, Scott C. Shi, Pei-Yong |
| author_facet | Liu, Yang Zhang, Xianwen Liu, Jianying Xia, Hongjie Zou, Jing Muruato, Antonio E. Periasamy, Sivakumar Kurhade, Chaitanya Plante, Jessica A. Bopp, Nathen E. Kalveram, Birte Bukreyev, Alexander Ren, Ping Wang, Tian Menachery, Vineet D. Plante, Kenneth S. Xie, Xuping Weaver, Scott C. Shi, Pei-Yong |
| author_sort | Liu, Yang |
| collection | PubMed |
| description | We report a live-attenuated SARS-CoV-2 vaccine candidate with (i) re-engineered viral transcription regulator sequences and (ii) deleted open-reading-frames (ORF) 3, 6, 7, and 8 (∆3678). The ∆3678 virus replicates about 7,500-fold lower than wild-type SARS-CoV-2 on primary human airway cultures, but restores its replication on interferon-deficient Vero-E6 cells that are approved for vaccine production. The ∆3678 virus is highly attenuated in both hamster and K18-hACE2 mouse models. A single-dose immunization of the ∆3678 virus protects hamsters from wild-type virus challenge and transmission. Among the deleted ORFs in the ∆3678 virus, ORF3a accounts for the most attenuation through antagonizing STAT1 phosphorylation during type-I interferon signaling. We also developed an mNeonGreen reporter ∆3678 virus for high-throughput neutralization and antiviral testing. Altogether, the results suggest that ∆3678 SARS-CoV-2 may serve as a live-attenuated vaccine candidate and a research tool for potential biosafety level-2 use. |
| format | Online Article Text |
| id | pubmed-9326133 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-93261332022-07-27 A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions Liu, Yang Zhang, Xianwen Liu, Jianying Xia, Hongjie Zou, Jing Muruato, Antonio E. Periasamy, Sivakumar Kurhade, Chaitanya Plante, Jessica A. Bopp, Nathen E. Kalveram, Birte Bukreyev, Alexander Ren, Ping Wang, Tian Menachery, Vineet D. Plante, Kenneth S. Xie, Xuping Weaver, Scott C. Shi, Pei-Yong Nat Commun Article We report a live-attenuated SARS-CoV-2 vaccine candidate with (i) re-engineered viral transcription regulator sequences and (ii) deleted open-reading-frames (ORF) 3, 6, 7, and 8 (∆3678). The ∆3678 virus replicates about 7,500-fold lower than wild-type SARS-CoV-2 on primary human airway cultures, but restores its replication on interferon-deficient Vero-E6 cells that are approved for vaccine production. The ∆3678 virus is highly attenuated in both hamster and K18-hACE2 mouse models. A single-dose immunization of the ∆3678 virus protects hamsters from wild-type virus challenge and transmission. Among the deleted ORFs in the ∆3678 virus, ORF3a accounts for the most attenuation through antagonizing STAT1 phosphorylation during type-I interferon signaling. We also developed an mNeonGreen reporter ∆3678 virus for high-throughput neutralization and antiviral testing. Altogether, the results suggest that ∆3678 SARS-CoV-2 may serve as a live-attenuated vaccine candidate and a research tool for potential biosafety level-2 use. Nature Publishing Group UK 2022-07-27 /pmc/articles/PMC9326133/ /pubmed/35896528 http://dx.doi.org/10.1038/s41467-022-31930-z Text en © The Author(s) 2022, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Liu, Yang Zhang, Xianwen Liu, Jianying Xia, Hongjie Zou, Jing Muruato, Antonio E. Periasamy, Sivakumar Kurhade, Chaitanya Plante, Jessica A. Bopp, Nathen E. Kalveram, Birte Bukreyev, Alexander Ren, Ping Wang, Tian Menachery, Vineet D. Plante, Kenneth S. Xie, Xuping Weaver, Scott C. Shi, Pei-Yong A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions |
| title | A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions |
| title_full | A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions |
| title_fullStr | A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions |
| title_full_unstemmed | A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions |
| title_short | A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions |
| title_sort | live-attenuated sars-cov-2 vaccine candidate with accessory protein deletions |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326133/ https://www.ncbi.nlm.nih.gov/pubmed/35896528 http://dx.doi.org/10.1038/s41467-022-31930-z |
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