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Nat Commun. 2017 Feb 13;8:14158. doi: 10.1038/ncomms14158.

Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state.

Author information

1
Medical Biotechnology Center, VIB, Technologiepark 927, Ghent B-9052, Belgium.
2
Department of Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium.
3
Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755-3844, USA.
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
5
Centro Nacional de Microbiología and CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain.

Abstract

Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV.

PMID:
28194013
PMCID:
PMC5316805
DOI:
10.1038/ncomms14158
[Indexed for MEDLINE]
Free PMC Article

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