Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein.
Immunity
; 55(9): 1710-1724.e8, 2022 09 13.
Article
en En
| MEDLINE
| ID: mdl-35944529
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Infecciones del Sistema Respiratorio
/
Metapneumovirus
/
Anticuerpos Neutralizantes
/
Anticuerpos Antivirales
Límite:
Adult
/
Aged
/
Animals
/
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article