Stabilized coronavirus spike stem elicits a broadly protective antibody

Summary: 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 r...

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Autores principales:	Ching-Lin Hsieh, Anne P. Werner, Sarah R. Leist, Laura J. Stevens, Ester Falconer, Jory A. Goldsmith, Chia-Wei Chou, Olubukola M. Abiona, Ande West, Kathryn Westendorf, Krithika Muthuraman, Ethan J. Fritch, Kenneth H. Dinnon, III, Alexandra Schäfer, Mark R. Denison, James D. Chappell, Ralph S. Baric, Barney S. Graham, Kizzmekia S. Corbett, Jason S. McLellan
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	coronaviruses (CoV) spike (S) glycoprotein stem stabilization cross-reactivity protective antibodies protective antigens Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/af2791637eea401ba71a9731ca3cb5c0
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spelling	oai:doaj.org-article:af2791637eea401ba71a9731ca3cb5c02021-11-04T04:29:18ZStabilized coronavirus spike stem elicits a broadly protective antibody2211-124710.1016/j.celrep.2021.109929https://doaj.org/article/af2791637eea401ba71a9731ca3cb5c02021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721014029https://doaj.org/toc/2211-1247Summary: 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.Ching-Lin HsiehAnne P. WernerSarah R. LeistLaura J. StevensEster FalconerJory A. GoldsmithChia-Wei ChouOlubukola M. AbionaAnde WestKathryn WestendorfKrithika MuthuramanEthan J. FritchKenneth H. Dinnon, IIIAlexandra SchäferMark R. DenisonJames D. ChappellRalph S. BaricBarney S. GrahamKizzmekia S. CorbettJason S. McLellanElsevierarticlecoronaviruses (CoV)spike (S) glycoproteinstem stabilizationcross-reactivityprotective antibodiesprotective antigensBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109929- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	coronaviruses (CoV) spike (S) glycoprotein stem stabilization cross-reactivity protective antibodies protective antigens Biology (General) QH301-705.5
spellingShingle	coronaviruses (CoV) spike (S) glycoprotein stem stabilization cross-reactivity protective antibodies protective antigens Biology (General) QH301-705.5 Ching-Lin Hsieh Anne P. Werner Sarah R. Leist Laura J. Stevens Ester Falconer Jory A. Goldsmith Chia-Wei Chou Olubukola M. Abiona Ande West Kathryn Westendorf Krithika Muthuraman Ethan J. Fritch Kenneth H. Dinnon, III Alexandra Schäfer Mark R. Denison James D. Chappell Ralph S. Baric Barney S. Graham Kizzmekia S. Corbett Jason S. McLellan Stabilized coronavirus spike stem elicits a broadly protective antibody
description	Summary: 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	article
author	Ching-Lin Hsieh Anne P. Werner Sarah R. Leist Laura J. Stevens Ester Falconer Jory A. Goldsmith Chia-Wei Chou Olubukola M. Abiona Ande West Kathryn Westendorf Krithika Muthuraman Ethan J. Fritch Kenneth H. Dinnon, III Alexandra Schäfer Mark R. Denison James D. Chappell Ralph S. Baric Barney S. Graham Kizzmekia S. Corbett Jason S. McLellan
author_facet	Ching-Lin Hsieh Anne P. Werner Sarah R. Leist Laura J. Stevens Ester Falconer Jory A. Goldsmith Chia-Wei Chou Olubukola M. Abiona Ande West Kathryn Westendorf Krithika Muthuraman Ethan J. Fritch Kenneth H. Dinnon, III Alexandra Schäfer Mark R. Denison James D. Chappell Ralph S. Baric Barney S. Graham Kizzmekia S. Corbett Jason S. McLellan
author_sort	Ching-Lin Hsieh
title	Stabilized coronavirus spike stem elicits a broadly protective antibody
title_short	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_sort	stabilized coronavirus spike stem elicits a broadly protective antibody
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/af2791637eea401ba71a9731ca3cb5c0
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Stabilized coronavirus spike stem elicits a broadly protective antibody

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