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Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) marks the third novel β-coronavirus to cause significant human mortality in the last two decades. Although vaccines are available, too few have been administered worldwide to keep the virus in check and to prevent mutations leading to immu...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302814/ https://www.ncbi.nlm.nih.gov/pubmed/35862475 http://dx.doi.org/10.1371/journal.ppat.1010691 |
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author | Piepenbrink, Michael S. Park, Jun-Gyu Deshpande, Ashlesha Loos, Andreas Ye, Chengjin Basu, Madhubanti Sarkar, Sanghita Khalil, Ahmed Magdy Chauvin, David Woo, Jennifer Lovalenti, Philip Erdmann, Nathaniel B. Goepfert, Paul A. Truong, Vu L. Bowen, Richard A. Walter, Mark R. Martinez-Sobrido, Luis Kobie, James J. |
author_facet | Piepenbrink, Michael S. Park, Jun-Gyu Deshpande, Ashlesha Loos, Andreas Ye, Chengjin Basu, Madhubanti Sarkar, Sanghita Khalil, Ahmed Magdy Chauvin, David Woo, Jennifer Lovalenti, Philip Erdmann, Nathaniel B. Goepfert, Paul A. Truong, Vu L. Bowen, Richard A. Walter, Mark R. Martinez-Sobrido, Luis Kobie, James J. |
author_sort | Piepenbrink, Michael S. |
collection | PubMed |
description | Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) marks the third novel β-coronavirus to cause significant human mortality in the last two decades. Although vaccines are available, too few have been administered worldwide to keep the virus in check and to prevent mutations leading to immune escape. To determine if antibodies could be identified with universal coronavirus activity, plasma from convalescent subjects was screened for IgG against a stabilized pre-fusion SARS-CoV-2 spike S2 domain, which is highly conserved between human β-coronavirus. From these subjects, several S2-specific human monoclonal antibodies (hmAbs) were developed that neutralized SARS-CoV-2 with recognition of all variants of concern (VoC) tested (Beta, Gamma, Delta, Epsilon, and Omicron). The hmAb 1249A8 emerged as the most potent and broad hmAb, able to recognize all human β-coronavirus and neutralize SARS-CoV and MERS-CoV. 1249A8 demonstrated significant prophylactic activity in K18 hACE2 mice infected with SARS-CoV-2 lineage A and lineage B Beta, and Omicron VoC. 1249A8 delivered as a single 4 mg/kg intranasal (i.n.) dose to hamsters 12 hours following infection with SARS-CoV-2 Delta protected them from weight loss, with therapeutic activity further enhanced when combined with 1213H7, an S1-specific neutralizing hmAb. As little as 2 mg/kg of 1249A8 i.n. dose 12 hours following infection with SARS-CoV Urbani strain, protected hamsters from weight loss and significantly reduced upper and lower respiratory viral burden. These results indicate in vivo cooperativity between S1 and S2 specific neutralizing hmAbs and that potent universal coronavirus neutralizing mAbs with therapeutic potential can be induced in humans and can guide universal coronavirus vaccine development. |
format | Online Article Text |
id | pubmed-9302814 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-93028142022-07-22 Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody Piepenbrink, Michael S. Park, Jun-Gyu Deshpande, Ashlesha Loos, Andreas Ye, Chengjin Basu, Madhubanti Sarkar, Sanghita Khalil, Ahmed Magdy Chauvin, David Woo, Jennifer Lovalenti, Philip Erdmann, Nathaniel B. Goepfert, Paul A. Truong, Vu L. Bowen, Richard A. Walter, Mark R. Martinez-Sobrido, Luis Kobie, James J. PLoS Pathog Research Article Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) marks the third novel β-coronavirus to cause significant human mortality in the last two decades. Although vaccines are available, too few have been administered worldwide to keep the virus in check and to prevent mutations leading to immune escape. To determine if antibodies could be identified with universal coronavirus activity, plasma from convalescent subjects was screened for IgG against a stabilized pre-fusion SARS-CoV-2 spike S2 domain, which is highly conserved between human β-coronavirus. From these subjects, several S2-specific human monoclonal antibodies (hmAbs) were developed that neutralized SARS-CoV-2 with recognition of all variants of concern (VoC) tested (Beta, Gamma, Delta, Epsilon, and Omicron). The hmAb 1249A8 emerged as the most potent and broad hmAb, able to recognize all human β-coronavirus and neutralize SARS-CoV and MERS-CoV. 1249A8 demonstrated significant prophylactic activity in K18 hACE2 mice infected with SARS-CoV-2 lineage A and lineage B Beta, and Omicron VoC. 1249A8 delivered as a single 4 mg/kg intranasal (i.n.) dose to hamsters 12 hours following infection with SARS-CoV-2 Delta protected them from weight loss, with therapeutic activity further enhanced when combined with 1213H7, an S1-specific neutralizing hmAb. As little as 2 mg/kg of 1249A8 i.n. dose 12 hours following infection with SARS-CoV Urbani strain, protected hamsters from weight loss and significantly reduced upper and lower respiratory viral burden. These results indicate in vivo cooperativity between S1 and S2 specific neutralizing hmAbs and that potent universal coronavirus neutralizing mAbs with therapeutic potential can be induced in humans and can guide universal coronavirus vaccine development. Public Library of Science 2022-07-21 /pmc/articles/PMC9302814/ /pubmed/35862475 http://dx.doi.org/10.1371/journal.ppat.1010691 Text en © 2022 Piepenbrink et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Piepenbrink, Michael S. Park, Jun-Gyu Deshpande, Ashlesha Loos, Andreas Ye, Chengjin Basu, Madhubanti Sarkar, Sanghita Khalil, Ahmed Magdy Chauvin, David Woo, Jennifer Lovalenti, Philip Erdmann, Nathaniel B. Goepfert, Paul A. Truong, Vu L. Bowen, Richard A. Walter, Mark R. Martinez-Sobrido, Luis Kobie, James J. Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody |
title | Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody |
title_full | Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody |
title_fullStr | Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody |
title_full_unstemmed | Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody |
title_short | Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody |
title_sort | potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a spike s2 domain-specific human neutralizing monoclonal antibody |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302814/ https://www.ncbi.nlm.nih.gov/pubmed/35862475 http://dx.doi.org/10.1371/journal.ppat.1010691 |
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