2026-05-22T00:39:50Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/160322025-05-23T09:10:02Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Rappazzo, C Garrett
author
Hsieh, Ching-Lin
author
Rush, Scott A
author
Esterman, Emma S
author
Delgado-Romero, Teresa
author
Geoghegan, James C
author
Wec, Anna Z
author
Sakharkar, Mrunal
author
Mas-Lloret, Vicente
author
McLellan, Jason S
author
Walker, Laura M
funder
NIH - National Cancer Institute (NCI) (Estados Unidos)
funder
Welch Foundation
2023-05-09T11:58:29Z
2023-05-09T11:58:29Z
2022-09-13
Immunity. 2022 Sep 13;55(9):1710-1724.e8.
10.1016/j.immuni.2022.07.003
1097-4180
Immunity
35944529
http://hdl.handle.net/20.500.12105/16032
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.
eng
Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein
research article
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URL
https://repisalud.isciii.es/bitstreams/104bc743-1187-4f05-9aef-8489c36dc3de/download
File
MD5
11cfeae09da8e390bb76cbae5e73a65e
3775843
application/pdf
PotentlyNeutralizingProtectiveAnti-human_2022.pdf
URL
https://repisalud.isciii.es/bitstreams/6e14b1ed-66f2-4c5c-859e-9ff4ef3ec6de/download
File
MD5
207a17f8da3000c585698e4977a71c57
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text/plain
PotentlyNeutralizingProtectiveAnti-human_2022.pdf.txt