Murine Monoclonal Antibodies against the Receptor Binding Domain of SARS-CoV-2 Neutralize Authentic Wild-Type SARS-CoV-2 as Well as B.1.1.7 and B.1.351 Viruses and Protect <italic toggle="yes">In Vivo</italic> in a Mouse Model in a Neutralization-Dependent Manner

ABSTRACT After first emerging in late 2019 in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has since caused a pandemic leading to millions of infections and deaths worldwide. Vaccines have been developed and authorized, but the supply of these vaccines is currently limited. Wi...

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Autores principales:	Fatima Amanat, Shirin Strohmeier, Wen-Hsin Lee, Sandhya Bangaru, Andrew B. Ward, Lynda Coughlan, Florian Krammer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	RBD SARS-CoV-2 monoclonal antibodies Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5a475d998e784aa6a06bf88698017360
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spelling	oai:doaj.org-article:5a475d998e784aa6a06bf886980173602021-11-10T18:37:50ZMurine Monoclonal Antibodies against the Receptor Binding Domain of SARS-CoV-2 Neutralize Authentic Wild-Type SARS-CoV-2 as Well as B.1.1.7 and B.1.351 Viruses and Protect <italic toggle="yes">In Vivo</italic> in a Mouse Model in a Neutralization-Dependent Manner10.1128/mBio.01002-212150-7511https://doaj.org/article/5a475d998e784aa6a06bf886980173602021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01002-21https://doaj.org/toc/2150-7511ABSTRACT After first emerging in late 2019 in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has since caused a pandemic leading to millions of infections and deaths worldwide. Vaccines have been developed and authorized, but the supply of these vaccines is currently limited. With new variants of the virus now emerging and spreading globally, it is essential to develop therapeutics that are broadly protective and bind conserved epitopes in the receptor binding domain (RBD) or the full-length spike protein of SARS-CoV-2. In this study, we generated mouse monoclonal antibodies (MAbs) against different epitopes on the RBD and assessed binding and neutralization of authentic SARS-CoV-2. We demonstrate that antibodies with neutralizing activity, but not nonneutralizing antibodies, lower viral titers in the lungs when administered in a prophylactic setting in vivo in a mouse challenge model. In addition, most of the MAbs cross-neutralize the B.1.351 as well as the B.1.1.7 variant in vitro. IMPORTANCE Cross-neutralization of SARS-CoV-2 variants by RBD-targeting antibodies is still not well understood, and very little is known about the potential protective effect of nonneutralizing antibodies in vivo. Using a panel of mouse monoclonal antibodies, we investigate both of these points.Fatima AmanatShirin StrohmeierWen-Hsin LeeSandhya BangaruAndrew B. WardLynda CoughlanFlorian KrammerAmerican Society for MicrobiologyarticleRBDSARS-CoV-2monoclonal antibodiesMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	RBD SARS-CoV-2 monoclonal antibodies Microbiology QR1-502
spellingShingle	RBD SARS-CoV-2 monoclonal antibodies Microbiology QR1-502 Fatima Amanat Shirin Strohmeier Wen-Hsin Lee Sandhya Bangaru Andrew B. Ward Lynda Coughlan Florian Krammer Murine Monoclonal Antibodies against the Receptor Binding Domain of SARS-CoV-2 Neutralize Authentic Wild-Type SARS-CoV-2 as Well as B.1.1.7 and B.1.351 Viruses and Protect <italic toggle="yes">In Vivo</italic> in a Mouse Model in a Neutralization-Dependent Manner
description	ABSTRACT After first emerging in late 2019 in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has since caused a pandemic leading to millions of infections and deaths worldwide. Vaccines have been developed and authorized, but the supply of these vaccines is currently limited. With new variants of the virus now emerging and spreading globally, it is essential to develop therapeutics that are broadly protective and bind conserved epitopes in the receptor binding domain (RBD) or the full-length spike protein of SARS-CoV-2. In this study, we generated mouse monoclonal antibodies (MAbs) against different epitopes on the RBD and assessed binding and neutralization of authentic SARS-CoV-2. We demonstrate that antibodies with neutralizing activity, but not nonneutralizing antibodies, lower viral titers in the lungs when administered in a prophylactic setting in vivo in a mouse challenge model. In addition, most of the MAbs cross-neutralize the B.1.351 as well as the B.1.1.7 variant in vitro. IMPORTANCE Cross-neutralization of SARS-CoV-2 variants by RBD-targeting antibodies is still not well understood, and very little is known about the potential protective effect of nonneutralizing antibodies in vivo. Using a panel of mouse monoclonal antibodies, we investigate both of these points.
format	article
author	Fatima Amanat Shirin Strohmeier Wen-Hsin Lee Sandhya Bangaru Andrew B. Ward Lynda Coughlan Florian Krammer
author_facet	Fatima Amanat Shirin Strohmeier Wen-Hsin Lee Sandhya Bangaru Andrew B. Ward Lynda Coughlan Florian Krammer
author_sort	Fatima Amanat
title	Murine Monoclonal Antibodies against the Receptor Binding Domain of SARS-CoV-2 Neutralize Authentic Wild-Type SARS-CoV-2 as Well as B.1.1.7 and B.1.351 Viruses and Protect <italic toggle="yes">In Vivo</italic> in a Mouse Model in a Neutralization-Dependent Manner
title_short	Murine Monoclonal Antibodies against the Receptor Binding Domain of SARS-CoV-2 Neutralize Authentic Wild-Type SARS-CoV-2 as Well as B.1.1.7 and B.1.351 Viruses and Protect <italic toggle="yes">In Vivo</italic> in a Mouse Model in a Neutralization-Dependent Manner
title_full	Murine Monoclonal Antibodies against the Receptor Binding Domain of SARS-CoV-2 Neutralize Authentic Wild-Type SARS-CoV-2 as Well as B.1.1.7 and B.1.351 Viruses and Protect <italic toggle="yes">In Vivo</italic> in a Mouse Model in a Neutralization-Dependent Manner
title_fullStr	Murine Monoclonal Antibodies against the Receptor Binding Domain of SARS-CoV-2 Neutralize Authentic Wild-Type SARS-CoV-2 as Well as B.1.1.7 and B.1.351 Viruses and Protect <italic toggle="yes">In Vivo</italic> in a Mouse Model in a Neutralization-Dependent Manner
title_full_unstemmed	Murine Monoclonal Antibodies against the Receptor Binding Domain of SARS-CoV-2 Neutralize Authentic Wild-Type SARS-CoV-2 as Well as B.1.1.7 and B.1.351 Viruses and Protect <italic toggle="yes">In Vivo</italic> in a Mouse Model in a Neutralization-Dependent Manner
title_sort	murine monoclonal antibodies against the receptor binding domain of sars-cov-2 neutralize authentic wild-type sars-cov-2 as well as b.1.1.7 and b.1.351 viruses and protect <italic toggle="yes">in vivo</italic> in a mouse model in a neutralization-dependent manner
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/5a475d998e784aa6a06bf88698017360
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Murine Monoclonal Antibodies against the Receptor Binding Domain of SARS-CoV-2 Neutralize Authentic Wild-Type SARS-CoV-2 as Well as B.1.1.7 and B.1.351 Viruses and Protect <italic toggle="yes">In Vivo</italic> in a Mouse Model in a Neutralization-Dependent Manner

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