TY - JOUR
T1 - A Candidate Therapeutic Monoclonal Antibody Inhibits Both HRSV and HMPV Replication in Mice
AU - Fausther-Bovendo, Hugues
AU - Hamelin, Marie Eve
AU - Carbonneau, Julie
AU - Venable, Marie Christine
AU - Checkmahomed, Liva
AU - Lavoie, Pierre Olivier
AU - Ouellet, Marie Ève
AU - Boivin, Guy
AU - D’Aoust, Marc André
AU - Kobinger, Gary P.
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
KW - HMPV
KW - HRSV
KW - therapeutic antibodies
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U2 - 10.3390/biomedicines10102516
DO - 10.3390/biomedicines10102516
M3 - Article
AN - SCOPUS:85140581041
SN - 2227-9059
VL - 10
JO - Biomedicines
JF - Biomedicines
IS - 10
M1 - 2516
ER -