Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/16032
Título
Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein
Autor(es)
Fecha de publicación
2022-09-13
Cita
Immunity. 2022 Sep 13;55(9):1710-1724.e8.
Idioma
Inglés
Tipo de documento
journal article
Resumen
Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a high-throughput single-cell technology to interrogate memory B cell responses to the hMPV fusion (F) glycoprotein in young adult and elderly donors. Across all donors, the neutralizing antibody response was primarily directed to epitopes expressed on both pre- and post-fusion F conformations. However, we identified rare, highly potent broadly neutralizing antibodies that recognize pre-fusion-specific epitopes and structurally characterized an antibody that targets a site of vulnerability at the pre-fusion F trimer apex. Additionally, monotherapy with neutralizing antibodies targeting three distinct antigenic sites provided robust protection against lower respiratory tract infection in a small animal model. This study provides promising monoclonal antibody candidates for passive immunoprophylaxis and informs the rational design of hMPV vaccine immunogens.
MESH
Antibodies, Neutralizing | Antibodies, Viral | Metapneumovirus | Respiratory Tract Infections | Aged | Animals | Epitopes | Glycoproteins | Humans | Viral Fusion Proteins | Young Adult
Versión en línea
DOI
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