Profiling of hMPV F-specific antibodies isolated from human memory B cells

Xiao Xiao, Arthur Fridman, Lu Zhang, Pavlo Pristatsky, Eberhard Durr, Michael Minnier, Aimin Tang, Kara S. Cox, Zhiyun Wen, Renee Moore, Dongrui Tian, Jennifer D. Galli, Scott Cosmi, Michael J. Eddins, Nicole L. Sullivan, Xiaodong Yan, Andrew J. Bett, Hua-Poo Su, Kalpit A. Vora (), Zhifeng Chen () and Lan Zhang ()
Additional contact information
Xiao Xiao: Infectious Diseases and Vaccines Discovery, Merck & Co., Inc.
Arthur Fridman: Data Science and Scientific Informatics, Merck & Co., Inc.
Lu Zhang: Bioinformatics and Biomarker Research, MSD
Pavlo Pristatsky: Analytical Research and Development, Merck & Co., Inc.
Eberhard Durr: Infectious Diseases and Vaccines Discovery, Merck & Co., Inc.
Michael Minnier: AgileOne
Aimin Tang: Infectious Diseases and Vaccines Discovery, Merck & Co., Inc.
Kara S. Cox: Infectious Diseases and Vaccines Discovery, Merck & Co., Inc.
Zhiyun Wen: Infectious Diseases and Vaccines Discovery, Merck & Co., Inc.
Renee Moore: Discovery Biologics, Merck & Co., Inc.
Dongrui Tian: Wuxi Biortus Biosciences Co. Ltd.
Jennifer D. Galli: Infectious Diseases and Vaccines Discovery, Merck & Co., Inc.
Scott Cosmi: Eurofins PSS Insourcing Solutions
Michael J. Eddins: Computational and Structural Chemistry, Merck & Co., Inc.
Nicole L. Sullivan: Infectious Diseases and Vaccines Discovery, Merck & Co., Inc.
Xiaodong Yan: Wuxi Biortus Biosciences Co. Ltd.
Andrew J. Bett: Infectious Diseases and Vaccines Discovery, Merck & Co., Inc.
Hua-Poo Su: Computational and Structural Chemistry, Merck & Co., Inc.
Kalpit A. Vora: Infectious Diseases and Vaccines Discovery, Merck & Co., Inc.
Zhifeng Chen: Infectious Diseases and Vaccines Discovery, Merck & Co., Inc.
Lan Zhang: Infectious Diseases and Vaccines Discovery, Merck & Co., Inc.

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Human metapneumovirus (hMPV) belongs to the Pneumoviridae family and is closely related to respiratory syncytial virus (RSV). The surface fusion (F) glycoprotein mediates viral fusion and is the primary target of neutralizing antibodies against hMPV. Here we report 113 hMPV-F specific monoclonal antibodies (mAbs) isolated from memory B cells of human donors. We characterize the antibodies’ germline usage, epitopes, neutralization potencies, and binding specificities. We find that unlike RSV-F specific mAbs, antibody responses to hMPV F are less dominant against the apex of the antigen, and the majority of the potent neutralizing mAbs recognize epitopes on the side of hMPV F. Furthermore, neutralizing epitopes that differ from previously defined antigenic sites on RSV F are identified, and multiple binding modes of site V and II mAbs are discovered. Interestingly, mAbs that bind preferentially to the unprocessed prefusion F show poor neutralization potency. These results elucidate the immune recognition of hMPV infection and provide novel insights for future hMPV antibody and vaccine development.

Date: 2022
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DOI: 10.1038/s41467-022-30205-x

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