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Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses

BACKGROUND: The COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved COVID-19 vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. SARS-CoV-2 “variants of conc...

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Autores principales: Halfmann, Peter J., Frey, Steven J., Loeffler, Kathryn, Kuroda, Makoto, Maemura, Tadashi, Armbrust, Tammy, Yang, Jie E., Hou, Yixuan J., Baric, Ralph, Wright, Elizabeth R., Kawaoka, Yoshihiro, Kane, Ravi S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9651965/
https://www.ncbi.nlm.nih.gov/pubmed/36375316
http://dx.doi.org/10.1016/j.ebiom.2022.104341
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author Halfmann, Peter J.
Frey, Steven J.
Loeffler, Kathryn
Kuroda, Makoto
Maemura, Tadashi
Armbrust, Tammy
Yang, Jie E.
Hou, Yixuan J.
Baric, Ralph
Wright, Elizabeth R.
Kawaoka, Yoshihiro
Kane, Ravi S.
author_facet Halfmann, Peter J.
Frey, Steven J.
Loeffler, Kathryn
Kuroda, Makoto
Maemura, Tadashi
Armbrust, Tammy
Yang, Jie E.
Hou, Yixuan J.
Baric, Ralph
Wright, Elizabeth R.
Kawaoka, Yoshihiro
Kane, Ravi S.
author_sort Halfmann, Peter J.
collection PubMed
description BACKGROUND: The COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved COVID-19 vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. SARS-CoV-2 “variants of concern” have acquired mutations in this domain allowing them to evade vaccine-induced humoral immunity. Recent approaches to improve the breadth of protection beyond SARS-CoV-2 have required the use of mixtures of RBD antigens from different sarbecoviruses. It may therefore be beneficial to develop a vaccine in which the protective immune response targets a more conserved region of the S protein. METHODS: Here we have developed a vaccine based on the conserved S2 subunit of the S protein and optimized the adjuvant and immunization regimen in Syrian hamsters and BALB/c mice. We have characterized the efficacy of the vaccine against SARS-CoV-2 variants and other coronaviruses. FINDINGS: Immunization with S2-based constructs elicited a broadly cross-reactive IgG antibody response that recognized the spike proteins of not only SARS-CoV-2 variants, but also SARS-CoV-1, and the four endemic human coronaviruses. Importantly, immunization reduced virus titers in respiratory tissues in vaccinated animals challenged with SARS-CoV-2 variants B.1.351 (beta), B.1.617.2 (delta), and BA.1 (omicron) as well as a pangolin coronavirus. INTERPRETATION: These results suggest that S2-based constructs can elicit a broadly cross-reactive antibody response resulting in limited virus replication, thus providing a framework for designing vaccines that elicit broad protection against coronaviruses. FUNDING: 10.13039/100000002NIH, 10.13039/100009619Japan Agency for Medical Research and Development, Garry Betty/ V Foundation Chair Fund, and 10.13039/100000001NSF.
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spelling pubmed-96519652022-11-14 Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses Halfmann, Peter J. Frey, Steven J. Loeffler, Kathryn Kuroda, Makoto Maemura, Tadashi Armbrust, Tammy Yang, Jie E. Hou, Yixuan J. Baric, Ralph Wright, Elizabeth R. Kawaoka, Yoshihiro Kane, Ravi S. eBioMedicine Articles BACKGROUND: The COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved COVID-19 vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. SARS-CoV-2 “variants of concern” have acquired mutations in this domain allowing them to evade vaccine-induced humoral immunity. Recent approaches to improve the breadth of protection beyond SARS-CoV-2 have required the use of mixtures of RBD antigens from different sarbecoviruses. It may therefore be beneficial to develop a vaccine in which the protective immune response targets a more conserved region of the S protein. METHODS: Here we have developed a vaccine based on the conserved S2 subunit of the S protein and optimized the adjuvant and immunization regimen in Syrian hamsters and BALB/c mice. We have characterized the efficacy of the vaccine against SARS-CoV-2 variants and other coronaviruses. FINDINGS: Immunization with S2-based constructs elicited a broadly cross-reactive IgG antibody response that recognized the spike proteins of not only SARS-CoV-2 variants, but also SARS-CoV-1, and the four endemic human coronaviruses. Importantly, immunization reduced virus titers in respiratory tissues in vaccinated animals challenged with SARS-CoV-2 variants B.1.351 (beta), B.1.617.2 (delta), and BA.1 (omicron) as well as a pangolin coronavirus. INTERPRETATION: These results suggest that S2-based constructs can elicit a broadly cross-reactive antibody response resulting in limited virus replication, thus providing a framework for designing vaccines that elicit broad protection against coronaviruses. FUNDING: 10.13039/100000002NIH, 10.13039/100009619Japan Agency for Medical Research and Development, Garry Betty/ V Foundation Chair Fund, and 10.13039/100000001NSF. Elsevier 2022-11-11 /pmc/articles/PMC9651965/ /pubmed/36375316 http://dx.doi.org/10.1016/j.ebiom.2022.104341 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Articles
Halfmann, Peter J.
Frey, Steven J.
Loeffler, Kathryn
Kuroda, Makoto
Maemura, Tadashi
Armbrust, Tammy
Yang, Jie E.
Hou, Yixuan J.
Baric, Ralph
Wright, Elizabeth R.
Kawaoka, Yoshihiro
Kane, Ravi S.
Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses
title Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses
title_full Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses
title_fullStr Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses
title_full_unstemmed Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses
title_short Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses
title_sort multivalent s2-based vaccines provide broad protection against sars-cov-2 variants of concern and pangolin coronaviruses
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9651965/
https://www.ncbi.nlm.nih.gov/pubmed/36375316
http://dx.doi.org/10.1016/j.ebiom.2022.104341
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