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Stabilized coronavirus spike stem elicits a broadly protective antibody
Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respirator...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s).
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519809/ https://www.ncbi.nlm.nih.gov/pubmed/34710354 http://dx.doi.org/10.1016/j.celrep.2021.109929 |
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author | Hsieh, Ching-Lin Werner, Anne P. Leist, Sarah R. Stevens, Laura J. Falconer, Ester Goldsmith, Jory A. Chou, Chia-Wei Abiona, Olubukola M. West, Ande Westendorf, Kathryn Muthuraman, Krithika Fritch, Ethan J. Dinnon, Kenneth H. Schäfer, Alexandra Denison, Mark R. Chappell, James D. Baric, Ralph S. Graham, Barney S. Corbett, Kizzmekia S. McLellan, Jason S. |
author_facet | Hsieh, Ching-Lin Werner, Anne P. Leist, Sarah R. Stevens, Laura J. Falconer, Ester Goldsmith, Jory A. Chou, Chia-Wei Abiona, Olubukola M. West, Ande Westendorf, Kathryn Muthuraman, Krithika Fritch, Ethan J. Dinnon, Kenneth H. Schäfer, Alexandra Denison, Mark R. Chappell, James D. Baric, Ralph S. Graham, Barney S. Corbett, Kizzmekia S. McLellan, Jason S. |
author_sort | Hsieh, Ching-Lin |
collection | PubMed |
description | Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and develop stabilized stem (SS) antigens. Vaccination with MERS SS elicits cross-reactive β-CoV antibody responses and protects mice against lethal MERS-CoV challenge. High-throughput screening of antibody-secreting cells from MERS SS-immunized mice led to the discovery of a panel of cross-reactive monoclonal antibodies. Among them, antibody IgG22 binds with high affinity to both MERS-CoV and severe acute respiratory syndrome (SARS)-CoV-2 S proteins, and a combination of electron microscopy and crystal structures localizes the epitope to a conserved coiled-coil region in the S2 subunit. Passive transfer of IgG22 protects mice against both MERS-CoV and SARS-CoV-2 challenge. Collectively, these results provide a proof of principle for cross-reactive CoV antibodies and inform the development of pan-CoV vaccines and therapeutic antibodies. |
format | Online Article Text |
id | pubmed-8519809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Author(s). |
record_format | MEDLINE/PubMed |
spelling | pubmed-85198092021-10-18 Stabilized coronavirus spike stem elicits a broadly protective antibody Hsieh, Ching-Lin Werner, Anne P. Leist, Sarah R. Stevens, Laura J. Falconer, Ester Goldsmith, Jory A. Chou, Chia-Wei Abiona, Olubukola M. West, Ande Westendorf, Kathryn Muthuraman, Krithika Fritch, Ethan J. Dinnon, Kenneth H. Schäfer, Alexandra Denison, Mark R. Chappell, James D. Baric, Ralph S. Graham, Barney S. Corbett, Kizzmekia S. McLellan, Jason S. Cell Rep Article Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and develop stabilized stem (SS) antigens. Vaccination with MERS SS elicits cross-reactive β-CoV antibody responses and protects mice against lethal MERS-CoV challenge. High-throughput screening of antibody-secreting cells from MERS SS-immunized mice led to the discovery of a panel of cross-reactive monoclonal antibodies. Among them, antibody IgG22 binds with high affinity to both MERS-CoV and severe acute respiratory syndrome (SARS)-CoV-2 S proteins, and a combination of electron microscopy and crystal structures localizes the epitope to a conserved coiled-coil region in the S2 subunit. Passive transfer of IgG22 protects mice against both MERS-CoV and SARS-CoV-2 challenge. Collectively, these results provide a proof of principle for cross-reactive CoV antibodies and inform the development of pan-CoV vaccines and therapeutic antibodies. The Author(s). 2021-11-02 2021-10-16 /pmc/articles/PMC8519809/ /pubmed/34710354 http://dx.doi.org/10.1016/j.celrep.2021.109929 Text en © 2021 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Hsieh, Ching-Lin Werner, Anne P. Leist, Sarah R. Stevens, Laura J. Falconer, Ester Goldsmith, Jory A. Chou, Chia-Wei Abiona, Olubukola M. West, Ande Westendorf, Kathryn Muthuraman, Krithika Fritch, Ethan J. Dinnon, Kenneth H. Schäfer, Alexandra Denison, Mark R. Chappell, James D. Baric, Ralph S. Graham, Barney S. Corbett, Kizzmekia S. McLellan, Jason S. Stabilized coronavirus spike stem elicits a broadly protective antibody |
title | Stabilized coronavirus spike stem elicits a broadly protective antibody |
title_full | Stabilized coronavirus spike stem elicits a broadly protective antibody |
title_fullStr | Stabilized coronavirus spike stem elicits a broadly protective antibody |
title_full_unstemmed | Stabilized coronavirus spike stem elicits a broadly protective antibody |
title_short | Stabilized coronavirus spike stem elicits a broadly protective antibody |
title_sort | stabilized coronavirus spike stem elicits a broadly protective antibody |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519809/ https://www.ncbi.nlm.nih.gov/pubmed/34710354 http://dx.doi.org/10.1016/j.celrep.2021.109929 |
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