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Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates
The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further r...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395824/ https://www.ncbi.nlm.nih.gov/pubmed/37531329 http://dx.doi.org/10.1371/journal.ppat.1011532 |
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author | Hermet, Paule Delache, Benoît Herate, Cecile Wolf, Esther Kivi, Gaily Juronen, Erkki Mumm, Karl Žusinaite, Eva Kainov, Denis Sankovski, Eve Virumäe, Kai Planken, Anu Merits, Andres Besaw, Jessica E. Yee, Ai Woon Morizumi, Takefumi Kim, Kyumhyuk Kuo, Anling Berriche, Asma Dereuddre-Bosquet, Nathalie Sconosciuti, Quentin Naninck, Thibaut Relouzat, Francis Cavarelli, Mariangela Ustav, Mart Wilson, Derek Ernst, Oliver P. Männik, Andres LeGrand, Roger Ustav, Mart |
author_facet | Hermet, Paule Delache, Benoît Herate, Cecile Wolf, Esther Kivi, Gaily Juronen, Erkki Mumm, Karl Žusinaite, Eva Kainov, Denis Sankovski, Eve Virumäe, Kai Planken, Anu Merits, Andres Besaw, Jessica E. Yee, Ai Woon Morizumi, Takefumi Kim, Kyumhyuk Kuo, Anling Berriche, Asma Dereuddre-Bosquet, Nathalie Sconosciuti, Quentin Naninck, Thibaut Relouzat, Francis Cavarelli, Mariangela Ustav, Mart Wilson, Derek Ernst, Oliver P. Männik, Andres LeGrand, Roger Ustav, Mart |
author_sort | Hermet, Paule |
collection | PubMed |
description | The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants. Furthermore, cumbersome systemic administration limits easy and broad access to such drugs. As well, concentrations of systemically administered antibodies in the mucosal epithelium, a primary site of initial infection, are dependent on neonatal Fc receptor mediated transport and require high drug concentrations. To reduce the viral load more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2 neutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-neutralizing properties. Administration of this antibody via a vibrating mesh nebulization device retained antibody integrity and resulted in effective distribution of the antibody in the upper and lower respiratory tract of non-human primates (NHP). In comparison with intravenous administration, significantly higher antibody concentrations can be obtained in the lung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This approach may reduce the barriers of access and uptake of antibody therapeutics in real-world clinical settings and provide a more effective blueprint for targeting existing and potentially emerging respiratory tract viruses. |
format | Online Article Text |
id | pubmed-10395824 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-103958242023-08-03 Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates Hermet, Paule Delache, Benoît Herate, Cecile Wolf, Esther Kivi, Gaily Juronen, Erkki Mumm, Karl Žusinaite, Eva Kainov, Denis Sankovski, Eve Virumäe, Kai Planken, Anu Merits, Andres Besaw, Jessica E. Yee, Ai Woon Morizumi, Takefumi Kim, Kyumhyuk Kuo, Anling Berriche, Asma Dereuddre-Bosquet, Nathalie Sconosciuti, Quentin Naninck, Thibaut Relouzat, Francis Cavarelli, Mariangela Ustav, Mart Wilson, Derek Ernst, Oliver P. Männik, Andres LeGrand, Roger Ustav, Mart PLoS Pathog Research Article The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants. Furthermore, cumbersome systemic administration limits easy and broad access to such drugs. As well, concentrations of systemically administered antibodies in the mucosal epithelium, a primary site of initial infection, are dependent on neonatal Fc receptor mediated transport and require high drug concentrations. To reduce the viral load more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2 neutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-neutralizing properties. Administration of this antibody via a vibrating mesh nebulization device retained antibody integrity and resulted in effective distribution of the antibody in the upper and lower respiratory tract of non-human primates (NHP). In comparison with intravenous administration, significantly higher antibody concentrations can be obtained in the lung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This approach may reduce the barriers of access and uptake of antibody therapeutics in real-world clinical settings and provide a more effective blueprint for targeting existing and potentially emerging respiratory tract viruses. Public Library of Science 2023-08-02 /pmc/articles/PMC10395824/ /pubmed/37531329 http://dx.doi.org/10.1371/journal.ppat.1011532 Text en © 2023 Hermet 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 Hermet, Paule Delache, Benoît Herate, Cecile Wolf, Esther Kivi, Gaily Juronen, Erkki Mumm, Karl Žusinaite, Eva Kainov, Denis Sankovski, Eve Virumäe, Kai Planken, Anu Merits, Andres Besaw, Jessica E. Yee, Ai Woon Morizumi, Takefumi Kim, Kyumhyuk Kuo, Anling Berriche, Asma Dereuddre-Bosquet, Nathalie Sconosciuti, Quentin Naninck, Thibaut Relouzat, Francis Cavarelli, Mariangela Ustav, Mart Wilson, Derek Ernst, Oliver P. Männik, Andres LeGrand, Roger Ustav, Mart Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates |
title | Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates |
title_full | Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates |
title_fullStr | Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates |
title_full_unstemmed | Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates |
title_short | Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates |
title_sort | broadly neutralizing humanized sars-cov-2 antibody binds to a conserved epitope on spike and provides antiviral protection through inhalation-based delivery in non-human primates |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395824/ https://www.ncbi.nlm.nih.gov/pubmed/37531329 http://dx.doi.org/10.1371/journal.ppat.1011532 |
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