Ballegeer, Marliesvan Scherpenzeel, Revina CDelgado-Romero, TeresaIglesias-Caballero, MariaGarcia-Barreno, BlancaPandey, ShubhamRush, Scott AKolkman, Joost AMas-Lloret, VicenteMcLellan, Jason SSaelens, Xavier2024-01-112024-01-112024mBio. 2024 Jan 16;15(1):e0212223.http://hdl.handle.net/20.500.12105/16942Human 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.engVoRhttp://creativecommons.org/licenses/by/4.0/Fusion proteinHuman metapneumovirusSingle-domain antibodyStructureAtribución 4.0 Internacional38117059e021222310.1128/mbio.02122-232150-7511mBioopen access