title: Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion.
abstract: Despite the medical importance of respiratory syncytial virus (RSV) infections, there is no vaccine or therapeutic agent available. Prophylactic administration of palivizumab, a humanized monoclonal RSV fusion (F) protein-specific antibody, can protect high-risk children. Previously, we have demonstrated that RSV can be neutralized by picomolar concentrations of a camelid immunoglobulin single-variable domain that binds the RSV protein F (F-VHHb nanobodies). Here, we investigated the mechanism by which these nanobodies neutralize RSV and tested their antiviral activity in vivo. We demonstrate that bivalent RSV F-specific nanobodies neutralize RSV infection by inhibiting fusion without affecting viral attachment. The ability of RSV F-specific nanobodies to protect against RSV infection was investigated in vivo. Intranasal administration of bivalent RSV F-specific nanobodies protected BALB/c mice from RSV infection, and associated pulmonary inflammation. Moreover, therapeutic treatment with these nanobodies after RSV infection could reduce viral replication and reduced pulmonary inflammation. Thus, nanobodies are promising therapeutic molecules for treatment of RSV.
authors: Department for Molecular Biomedical Research, VIB, Ghent University, Belgium.
authors: Bert
authors: B
authors: Schepens
authors: Lorena Itatí
authors: LI
authors: Ibañez
authors: Sarah
authors: S
authors: De Baets
authors: Anna
authors: A
authors: Hultberg
authors: Pieter
authors: P
authors: Bogaert
authors: Pieter
authors: P
authors: De Bleser
authors: Frederik
authors: F
authors: Vervalle
authors: Theo
authors: T
authors: Verrips
authors: José
authors: J
authors: Melero
authors: Wesly
authors: W
authors: Vandevelde
authors: Peter
authors: P
authors: Vanlandschoot
authors: Xavier
authors: X
authors: Saelens
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology*; D000998:Antiviral Agents / Q000276:immunology / Q000494:pharmacology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013997:Time Factors; D014760:Viral Fusion Proteins / Q000276:immunology; D019562:Viral Load / Q000187:drug effects; D053585:Virus Attachment / Q000187:drug effects*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000998:Antiviral Agents; D014760:Viral Fusion Proteins