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A Candidate Therapeutic Monoclonal Antibody Inhibits Both HRSV and HMPV Replication in Mice
Human metapneumovirus (HMPV) and human respiratory virus (HRSV) are two leading causes of acute respiratory tract infection in young children. While there is no licensed drug against HMPV, the monoclonal antibody (mAb) Palivizumab is approved against HRSV for prophylaxis use only. Novel therapeutics...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599547/ https://www.ncbi.nlm.nih.gov/pubmed/36289776 http://dx.doi.org/10.3390/biomedicines10102516 |
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author | Fausther-Bovendo, Hugues Hamelin, Marie-Eve Carbonneau, Julie Venable, Marie-Christine Checkmahomed, Liva Lavoie, Pierre-Olivier Ouellet, Marie-Ève Boivin, Guy D’Aoust, Marc-André Kobinger, Gary P. |
author_facet | Fausther-Bovendo, Hugues Hamelin, Marie-Eve Carbonneau, Julie Venable, Marie-Christine Checkmahomed, Liva Lavoie, Pierre-Olivier Ouellet, Marie-Ève Boivin, Guy D’Aoust, Marc-André Kobinger, Gary P. |
author_sort | Fausther-Bovendo, Hugues |
collection | PubMed |
description | Human metapneumovirus (HMPV) and human respiratory virus (HRSV) are two leading causes of acute respiratory tract infection in young children. While there is no licensed drug against HMPV, the monoclonal antibody (mAb) Palivizumab is approved against HRSV for prophylaxis use only. Novel therapeutics against both viruses are therefore needed. Here, we describe the identification of human mAbs targeting these viruses by using flow cytometry-based cell sorting. One hundred and two antibodies were initially identified from flow cytometry-based cell sorting as binding to the fusion protein from HRSV, HMPV or both. Of those, 95 were successfully produced in plants, purified and characterized for binding activity by ELISA and neutralization assays as well as by inhibition of virus replication in mice. Twenty-two highly reactive mAbs targeting either HRSV or HMPV were isolated. Of these, three mAbs inhibited replication in vivo of a single virus while one mAb could reduce both HRSV and HMPV titers in the lung. Overall, this study identifies several human mAbs with virus-specific therapeutic potential and a unique mAb with inhibitory activities against both HRSV and HMPV. |
format | Online Article Text |
id | pubmed-9599547 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95995472022-10-27 A Candidate Therapeutic Monoclonal Antibody Inhibits Both HRSV and HMPV Replication in Mice Fausther-Bovendo, Hugues Hamelin, Marie-Eve Carbonneau, Julie Venable, Marie-Christine Checkmahomed, Liva Lavoie, Pierre-Olivier Ouellet, Marie-Ève Boivin, Guy D’Aoust, Marc-André Kobinger, Gary P. Biomedicines Article Human metapneumovirus (HMPV) and human respiratory virus (HRSV) are two leading causes of acute respiratory tract infection in young children. While there is no licensed drug against HMPV, the monoclonal antibody (mAb) Palivizumab is approved against HRSV for prophylaxis use only. Novel therapeutics against both viruses are therefore needed. Here, we describe the identification of human mAbs targeting these viruses by using flow cytometry-based cell sorting. One hundred and two antibodies were initially identified from flow cytometry-based cell sorting as binding to the fusion protein from HRSV, HMPV or both. Of those, 95 were successfully produced in plants, purified and characterized for binding activity by ELISA and neutralization assays as well as by inhibition of virus replication in mice. Twenty-two highly reactive mAbs targeting either HRSV or HMPV were isolated. Of these, three mAbs inhibited replication in vivo of a single virus while one mAb could reduce both HRSV and HMPV titers in the lung. Overall, this study identifies several human mAbs with virus-specific therapeutic potential and a unique mAb with inhibitory activities against both HRSV and HMPV. MDPI 2022-10-08 /pmc/articles/PMC9599547/ /pubmed/36289776 http://dx.doi.org/10.3390/biomedicines10102516 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fausther-Bovendo, Hugues Hamelin, Marie-Eve Carbonneau, Julie Venable, Marie-Christine Checkmahomed, Liva Lavoie, Pierre-Olivier Ouellet, Marie-Ève Boivin, Guy D’Aoust, Marc-André Kobinger, Gary P. A Candidate Therapeutic Monoclonal Antibody Inhibits Both HRSV and HMPV Replication in Mice |
title | A Candidate Therapeutic Monoclonal Antibody Inhibits Both HRSV and HMPV Replication in Mice |
title_full | A Candidate Therapeutic Monoclonal Antibody Inhibits Both HRSV and HMPV Replication in Mice |
title_fullStr | A Candidate Therapeutic Monoclonal Antibody Inhibits Both HRSV and HMPV Replication in Mice |
title_full_unstemmed | A Candidate Therapeutic Monoclonal Antibody Inhibits Both HRSV and HMPV Replication in Mice |
title_short | A Candidate Therapeutic Monoclonal Antibody Inhibits Both HRSV and HMPV Replication in Mice |
title_sort | candidate therapeutic monoclonal antibody inhibits both hrsv and hmpv replication in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599547/ https://www.ncbi.nlm.nih.gov/pubmed/36289776 http://dx.doi.org/10.3390/biomedicines10102516 |
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