Download MendeleyA neutralizing single-domain antibody that targets the trimer interface of the human metapneumovirus fusion protein.
Ballegeer, M., van Scherpenzeel, R.C., Delgado, T., Iglesias-Caballero, M., Garcia Barreno, B., Pandey, S., Rush, S.A., Kolkman, J.A., Mas, V., McLellan, J.S., Saelens, X.(2024) mBio 15: e0212223-e0212223
- PubMed: 38117059
- DOI: https://doi.org/10.1128/mbio.02122-23
- Primary Citation of Related Structures:
8TW3 - PubMed 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.
Organizational Affiliation:
VIB Center for Medical Biotechnology, VIB, Ghent, Belgium.
