Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
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
_version_ 1784751716589109248
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
work_keys_str_mv AT piepenbrinkmichaels potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT parkjungyu potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT deshpandeashlesha potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT loosandreas potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT yechengjin potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT basumadhubanti potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT sarkarsanghita potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT khalilahmedmagdy potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT chauvindavid potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT woojennifer potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT lovalentiphilip potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT erdmannnathanielb potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT goepfertpaula potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT truongvul potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT bowenricharda potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT waltermarkr potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT martinezsobridoluis potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody
AT kobiejamesj potentuniversalbetacoronavirustherapeuticactivitymediatedbydirectrespiratoryadministrationofaspikes2domainspecifichumanneutralizingmonoclonalantibody