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

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 relevan...

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Detalhes bibliográficos
Autores: Rossey, Iebe, Gilman, Morgan S A, Kabeche, Stephanie C, Sedeyn, Koen, Wrapp, Daniel, Kanekiyo, Masaru, Chen, Man, Spitaels, Jan, Graham, Barney S, Schepens, Bert, McLellan, Jason S, Saelens, Xavier, Mas-Lloret, Vicente, Melero, Jose Antonio
Formato: artículo
Fecha de publicación:2017
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/10416
Acesso em linha:http://hdl.handle.net/20.500.12105/10416
Access Level:acceso abierto
Palavra-chave:Animals
Antibodies, Neutralizing
Camelids, New World
Chlorocebus aethiops
Humans
Mice
Monocytes
Protein Binding
Respiratory Syncytial Virus Infections
Respiratory Syncytial Virus, Human
Single-Domain Antibodies
T-Lymphocytes
Vero Cells
Viral Fusion Proteins
Virus Replication
Descrição
Resumo: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.

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