Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/16942
Title
A neutralizing single-domain antibody that targets the trimer interface of the human metapneumovirus fusion protein
Author(s)
Ballegeer, Marlies | van Scherpenzeel, Revina C | Delgado-Romero, Teresa ISCIII | Iglesias-Caballero, Maria ISCIII | Garcia-Barreno, Blanca ISCIII | Pandey, Shubham | Rush, Scott A | Kolkman, Joost A | Mas-Lloret, Vicente ISCIII | McLellan, Jason S | Saelens, Xavier
Date issued
2024
Citation
mBio. 2024 Jan 16;15(1):e0212223.
Language
Inglés
Document type
research article
Abstract
Human metapneumovirus (hMPV) is an important respiratory pathogen for which no licensed antivirals or vaccines exist. Single-domain antibodies represent promising antiviral biologics that can be easily produced and formatted. We describe the isolation and detailed characterization of two hMPV-neutralizing single-domain antibodies that are directed against the fusion protein F. One of these single-domain antibodies broadly neutralizes hMPV A and B strains, can prevent proteolytic maturation of F, and binds to an epitope in the F trimer interface. This suggests that hMPV pre-F undergoes trimer opening or "breathing" on infectious virions, exposing a vulnerable site for neutralizing antibodies. Finally, we show that this single-domain antibody, fused to a human IgG1 Fc, can protect cotton rats against hMPV replication, an important finding for potential future clinical applications.
Subject
Online version
DOI
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