2026-07-22T01:50:14Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/160322025-05-23T09:10:02Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc 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 author 2022-09-13 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. 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 Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein