Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784816621241499648
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
work_keys_str_mv AT faustherbovendohugues acandidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT hamelinmarieeve acandidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT carbonneaujulie acandidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT venablemariechristine acandidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT checkmahomedliva acandidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT lavoiepierreolivier acandidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT ouelletmarieeve acandidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT boivinguy acandidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT daoustmarcandre acandidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT kobingergaryp acandidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT faustherbovendohugues candidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT hamelinmarieeve candidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT carbonneaujulie candidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT venablemariechristine candidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT checkmahomedliva candidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT lavoiepierreolivier candidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT ouelletmarieeve candidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT boivinguy candidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT daoustmarcandre candidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice
AT kobingergaryp candidatetherapeuticmonoclonalantibodyinhibitsbothhrsvandhmpvreplicationinmice