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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...

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Autores principales: Shi, Juan, Wang, Gang, Zheng, Jian, Verma, Abhishek K., Guan, Xiaoqing, Malisheni, Moffat M., Geng, Qibin, Li, Fang, Perlman, Stanley, Du, Lanying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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.
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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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