Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein
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 inter...
| Authors: | , , , , , , , , , , |
|---|---|
| Format: | article |
| Publication Date: | 2022 |
| Country: | España |
| Institution: | Instituto de Salud Carlos III (ISCIII) |
| Repository: | Repisalud |
| Language: | English |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/16032 |
| Online Access: | http://hdl.handle.net/20.500.12105/16032 |
| Access Level: | Open access |
| Keyword: | Antibodies, Neutralizing Antibodies, Viral Metapneumovirus Respiratory Tract Infections Aged Animals Epitopes Glycoproteins Humans Viral Fusion Proteins Young Adult |
| Summary: | 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. |
|---|