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Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses
The emergence of current SARS-CoV-2 variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy(1–7). Development of broadly effective coronavirus vaccines that can mitigate these threats is needed(8,9)....
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8845431/ https://www.ncbi.nlm.nih.gov/pubmed/35169804 http://dx.doi.org/10.1101/2021.09.08.459480 |
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author | He, Wan-ting Musharrafieh, Rami Song, Ge Dueker, Katharina Tse, Longping V. Martinez, David R. Schäfer, Alexandra Callaghan, Sean Yong, Peter Beutler, Nathan Torres, Jonathan L. Volk, Reid M. Zhou, Panpan Yuan, Meng Liu, Hejun Anzanello, Fabio Capozzola, Tazio Parren, Mara Garcia, Elijah Rawlings, Stephen A. Smith, Davey M. Wilson, Ian A. Safonova, Yana Ward, Andrew B. Rogers, Thomas F. Baric, Ralph S. Gralinski, Lisa E. Burton, Dennis R. Andrabi, Raiees |
author_facet | He, Wan-ting Musharrafieh, Rami Song, Ge Dueker, Katharina Tse, Longping V. Martinez, David R. Schäfer, Alexandra Callaghan, Sean Yong, Peter Beutler, Nathan Torres, Jonathan L. Volk, Reid M. Zhou, Panpan Yuan, Meng Liu, Hejun Anzanello, Fabio Capozzola, Tazio Parren, Mara Garcia, Elijah Rawlings, Stephen A. Smith, Davey M. Wilson, Ian A. Safonova, Yana Ward, Andrew B. Rogers, Thomas F. Baric, Ralph S. Gralinski, Lisa E. Burton, Dennis R. Andrabi, Raiees |
author_sort | He, Wan-ting |
collection | PubMed |
description | The emergence of current SARS-CoV-2 variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy(1–7). Development of broadly effective coronavirus vaccines that can mitigate these threats is needed(8,9). Notably, several recent studies have revealed that vaccination of recovered COVID-19 donors results in enhanced nAb responses compared to SARS-CoV-2 infection or vaccination alone(10–13). Here, we utilized a targeted donor selection strategy to isolate a large panel of broadly neutralizing antibodies (bnAbs) to sarbecoviruses from two such donors. Many of the bnAbs are remarkably effective in neutralization against sarbecoviruses that use ACE2 for viral entry and a substantial fraction also show notable binding to non-ACE2-using sarbecoviruses. The bnAbs are equally effective against most SARS-CoV-2 VOCs and many neutralize the Omicron variant. Neutralization breadth is achieved by bnAb binding to epitopes on a relatively conserved face of the receptor binding domain (RBD) as opposed to strain-specific nAbs to the receptor binding site that are commonly elicited in SARS-CoV-2 infection and vaccination(14–18). Consistent with targeting of conserved sites, select RBD bnAbs exhibited in vivo protective efficacy against diverse SARS-like coronaviruses in a prophylaxis challenge model. The generation of a large panel of potent bnAbs provides new opportunities and choices for next-generation antibody prophylactic and therapeutic applications and, importantly, provides a molecular basis for effective design of pan-sarbecovirus vaccines. |
format | Online Article Text |
id | pubmed-8845431 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-88454312022-02-16 Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses He, Wan-ting Musharrafieh, Rami Song, Ge Dueker, Katharina Tse, Longping V. Martinez, David R. Schäfer, Alexandra Callaghan, Sean Yong, Peter Beutler, Nathan Torres, Jonathan L. Volk, Reid M. Zhou, Panpan Yuan, Meng Liu, Hejun Anzanello, Fabio Capozzola, Tazio Parren, Mara Garcia, Elijah Rawlings, Stephen A. Smith, Davey M. Wilson, Ian A. Safonova, Yana Ward, Andrew B. Rogers, Thomas F. Baric, Ralph S. Gralinski, Lisa E. Burton, Dennis R. Andrabi, Raiees bioRxiv Article The emergence of current SARS-CoV-2 variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy(1–7). Development of broadly effective coronavirus vaccines that can mitigate these threats is needed(8,9). Notably, several recent studies have revealed that vaccination of recovered COVID-19 donors results in enhanced nAb responses compared to SARS-CoV-2 infection or vaccination alone(10–13). Here, we utilized a targeted donor selection strategy to isolate a large panel of broadly neutralizing antibodies (bnAbs) to sarbecoviruses from two such donors. Many of the bnAbs are remarkably effective in neutralization against sarbecoviruses that use ACE2 for viral entry and a substantial fraction also show notable binding to non-ACE2-using sarbecoviruses. The bnAbs are equally effective against most SARS-CoV-2 VOCs and many neutralize the Omicron variant. Neutralization breadth is achieved by bnAb binding to epitopes on a relatively conserved face of the receptor binding domain (RBD) as opposed to strain-specific nAbs to the receptor binding site that are commonly elicited in SARS-CoV-2 infection and vaccination(14–18). Consistent with targeting of conserved sites, select RBD bnAbs exhibited in vivo protective efficacy against diverse SARS-like coronaviruses in a prophylaxis challenge model. The generation of a large panel of potent bnAbs provides new opportunities and choices for next-generation antibody prophylactic and therapeutic applications and, importantly, provides a molecular basis for effective design of pan-sarbecovirus vaccines. Cold Spring Harbor Laboratory 2022-02-08 /pmc/articles/PMC8845431/ /pubmed/35169804 http://dx.doi.org/10.1101/2021.09.08.459480 Text en https://creativecommons.org/licenses/by-nd/4.0/This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article He, Wan-ting Musharrafieh, Rami Song, Ge Dueker, Katharina Tse, Longping V. Martinez, David R. Schäfer, Alexandra Callaghan, Sean Yong, Peter Beutler, Nathan Torres, Jonathan L. Volk, Reid M. Zhou, Panpan Yuan, Meng Liu, Hejun Anzanello, Fabio Capozzola, Tazio Parren, Mara Garcia, Elijah Rawlings, Stephen A. Smith, Davey M. Wilson, Ian A. Safonova, Yana Ward, Andrew B. Rogers, Thomas F. Baric, Ralph S. Gralinski, Lisa E. Burton, Dennis R. Andrabi, Raiees Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses |
title | Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses |
title_full | Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses |
title_fullStr | Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses |
title_full_unstemmed | Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses |
title_short | Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses |
title_sort | targeted isolation of panels of diverse human protective broadly neutralizing antibodies against sars-like viruses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8845431/ https://www.ncbi.nlm.nih.gov/pubmed/35169804 http://dx.doi.org/10.1101/2021.09.08.459480 |
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