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A Candidate Therapeutic Monoclonal Antibody Inhibits Both HRSV and HMPV Replication in Mice
Hugues Fausther-Bovendo1,2, Marie-Eve Hamelin1, Julie Carbonneau1
1Department of Microbiology and Immunology, Faculty of Medicine, CHU de Quebec and Laval University, Quebec City, QC G1V 4G2, Canada.
Abstract:
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.
Insights
Researchers identified human monoclonal antibodies (mAbs) targeting respiratory viruses. One unique mAb demonstrated inhibitory activity against both human metapneumovirus (HMPV) and human respiratory syncytial virus (HRSV), offering potential for broad therapeutic use.
Area of Science:
- Virology and Immunology
- Therapeutic Antibody Development
Background:
- Human metapneumovirus (HMPV) and human respiratory syncytial virus (HRSV) are significant causes of pediatric respiratory infections.
- Existing treatments are limited, with Palivizumab approved only for HRSV prophylaxis, highlighting the need for novel HMPV and HRSV therapeutics.
Purpose of the Study:
- To identify and characterize human monoclonal antibodies (mAbs) with therapeutic potential against HMPV and HRSV.
- To discover mAbs capable of inhibiting viral replication in vitro and in vivo.
Main Methods:
- Utilized flow cytometry-based cell sorting to identify antibodies binding to HRSV and HMPV fusion proteins.
- Produced, purified, and characterized 95 antibodies using ELISA, neutralization assays, and in vivo mouse models.
- Assessed antibody binding activity, neutralization capacity, and inhibition of viral replication.
Main Results:
- Isolated 22 highly reactive human mAbs targeting either HRSV or HMPV.
- Identified three mAbs inhibiting single-virus replication in vivo.
- Discovered one unique mAb demonstrating inhibitory activity against both HRSV and HMPV in the lungs.
Conclusions:
- This study successfully identified several human mAbs with virus-specific therapeutic potential against HMPV and HRSV.
- A novel mAb with dual inhibitory activity against both viruses presents a promising candidate for broad-spectrum respiratory virus therapy.
