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Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern
The SARS-CoV-2 Omicron variant harbors more than 30 mutations in its spike (S) protein. Circulating Omicron subvariants, particularly BA5 and other variants of concern (VOCs), show increased resistance to COVID-19 vaccines that target the original S protein, calling for an urgent need for effective...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762654/ https://www.ncbi.nlm.nih.gov/pubmed/36535987 http://dx.doi.org/10.1038/s41541-022-00580-z |
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author | Shi, Juan Wang, Gang Zheng, Jian Verma, Abhishek K. Guan, Xiaoqing Malisheni, Moffat M. Geng, Qibin Li, Fang Perlman, Stanley Du, Lanying |
author_facet | Shi, Juan Wang, Gang Zheng, Jian Verma, Abhishek K. Guan, Xiaoqing Malisheni, Moffat M. Geng, Qibin Li, Fang Perlman, Stanley Du, Lanying |
author_sort | Shi, Juan |
collection | PubMed |
description | The SARS-CoV-2 Omicron variant harbors more than 30 mutations in its spike (S) protein. Circulating Omicron subvariants, particularly BA5 and other variants of concern (VOCs), show increased resistance to COVID-19 vaccines that target the original S protein, calling for an urgent need for effective vaccines to prevent multiple SARS-CoV-2 VOCs. Here, we evaluated the neutralizing activity and protection conferred by a BA1-S subunit vaccine when combined with or used as booster doses after, administration of wild-type S protein (WT-S). A WT-S/BA1-S cocktail, or WT-S prime and BA1-S boost, induced significantly higher neutralizing antibodies against pseudotyped Omicron BA1, BA2, BA2.12.1, and BA5 subvariants, and similar or higher neutralizing antibodies against the original SARS-CoV-2, than the WT-S protein alone. The WT-S/BA1-S cocktail also elicited higher or significantly higher neutralizing antibodies than the WT-S-prime-BA1-S boost, WT-S alone, or BA1-S alone against pseudotyped SARS-CoV-2 Alpha, Beta, Gamma, and Delta VOCs, and SARS-CoV, a closely related beta-coronavirus using the same receptor as SARS-CoV-2 for viral entry. By contrast, WT-S or BA1-S alone failed to induce potent neutralizing antibodies against all these viruses. Similar to the WT-S-prime-BA1-S boost, the WT-S/BA1-S cocktail completely protected mice against the lethal challenge of a Delta variant with negligible weight loss. Thus, we have identified an effective vaccination strategy that elicits potent, broadly, and durable neutralizing antibodies against circulating SARS-CoV-2 Omicron subvariants, other VOCs, original SARS-CoV-2, and SARS-CoV. These results will provide useful guidance for developing efficacious vaccines that inhibit current and future SARS-CoV-2 variants to control the COVID-19 pandemic. |
format | Online Article Text |
id | pubmed-9762654 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97626542022-12-20 Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern Shi, Juan Wang, Gang Zheng, Jian Verma, Abhishek K. Guan, Xiaoqing Malisheni, Moffat M. Geng, Qibin Li, Fang Perlman, Stanley Du, Lanying NPJ Vaccines Article The SARS-CoV-2 Omicron variant harbors more than 30 mutations in its spike (S) protein. Circulating Omicron subvariants, particularly BA5 and other variants of concern (VOCs), show increased resistance to COVID-19 vaccines that target the original S protein, calling for an urgent need for effective vaccines to prevent multiple SARS-CoV-2 VOCs. Here, we evaluated the neutralizing activity and protection conferred by a BA1-S subunit vaccine when combined with or used as booster doses after, administration of wild-type S protein (WT-S). A WT-S/BA1-S cocktail, or WT-S prime and BA1-S boost, induced significantly higher neutralizing antibodies against pseudotyped Omicron BA1, BA2, BA2.12.1, and BA5 subvariants, and similar or higher neutralizing antibodies against the original SARS-CoV-2, than the WT-S protein alone. The WT-S/BA1-S cocktail also elicited higher or significantly higher neutralizing antibodies than the WT-S-prime-BA1-S boost, WT-S alone, or BA1-S alone against pseudotyped SARS-CoV-2 Alpha, Beta, Gamma, and Delta VOCs, and SARS-CoV, a closely related beta-coronavirus using the same receptor as SARS-CoV-2 for viral entry. By contrast, WT-S or BA1-S alone failed to induce potent neutralizing antibodies against all these viruses. Similar to the WT-S-prime-BA1-S boost, the WT-S/BA1-S cocktail completely protected mice against the lethal challenge of a Delta variant with negligible weight loss. Thus, we have identified an effective vaccination strategy that elicits potent, broadly, and durable neutralizing antibodies against circulating SARS-CoV-2 Omicron subvariants, other VOCs, original SARS-CoV-2, and SARS-CoV. These results will provide useful guidance for developing efficacious vaccines that inhibit current and future SARS-CoV-2 variants to control the COVID-19 pandemic. Nature Publishing Group UK 2022-12-19 /pmc/articles/PMC9762654/ /pubmed/36535987 http://dx.doi.org/10.1038/s41541-022-00580-z Text en © The Author(s) 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 Shi, Juan Wang, Gang Zheng, Jian Verma, Abhishek K. Guan, Xiaoqing Malisheni, Moffat M. Geng, Qibin Li, Fang Perlman, Stanley Du, Lanying Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern |
title | Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern |
title_full | Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern |
title_fullStr | Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern |
title_full_unstemmed | Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern |
title_short | Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern |
title_sort | effective vaccination strategy using sars-cov-2 spike cocktail against omicron and other variants of concern |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762654/ https://www.ncbi.nlm.nih.gov/pubmed/36535987 http://dx.doi.org/10.1038/s41541-022-00580-z |
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