In:
Journal of Virology, American Society for Microbiology, Vol. 95, No. 11 ( 2021-05-10)
Kurzfassung:
Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease, especially in young children and the elderly. The fusion protein (F) exists in a pre- and postfusion conformation and is the main target of RSV-neutralizing antibodies. Highly potent RSV-neutralizing antibodies typically bind sites that are unique to the prefusion conformation of F. In this study, we screened a single-domain antibody (VHH) library derived from a llama immunized with prefusion-stabilized F and identified a prefusion F-specific VHH that can neutralize RSV A at subnanomolar concentrations. Structural analysis revealed that this VHH primarily binds to antigenic site I while also making contacts with residues in antigenic sites III and IV. This new VHH reveals a previously underappreciated membrane-proximal region sensitive to neutralization. IMPORTANCE RSV is an important respiratory pathogen. This study describes a prefusion F-specific VHH that primarily binds to antigenic site I of RSV F. This is the first time that a prefusion F-specific antibody that binds this site has been reported. In general, antibodies that bind to site I are poorly neutralizing, whereas the VHH described here neutralizes RSV A at subnanomolar concentrations. Our findings contribute to insights into the RSV F antigenic map.
Materialart:
Online-Ressource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.02279-20
Sprache:
Englisch
Verlag:
American Society for Microbiology
Publikationsdatum:
2021
ZDB Id:
1495529-5
