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Publication Abstract from PubMed

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.

Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein.,Rappazzo CG, Hsieh CL, Rush SA, Esterman ES, Delgado T, Geoghegan JC, Wec AZ, Sakharkar M, Mas V, McLellan JS, Walker LM Immunity. 2022 Sep 13;55(9):1710-1724.e8. doi: 10.1016/j.immuni.2022.07.003. Epub , 2022 Aug 8. PMID:35944529^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.