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

Author

Listed:
  • Xiao Xiao

    (Infectious Diseases and Vaccines Discovery, Merck & Co., Inc.
    Discovery Biologics, Merck & Co., Inc.
    MRL Postdoctoral Research Program; 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.)

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.

Suggested Citation

  • 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 & Mich, 2022. "Profiling of hMPV F-specific antibodies isolated from human memory B cells," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30205-x
    DOI: 10.1038/s41467-022-30205-x
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    1. Daiyin Tian & Michael B. Battles & Syed M. Moin & Man Chen & Kayvon Modjarrad & Azad Kumar & Masaru Kanekiyo & Kevin W. Graepel & Noor M. Taher & Anne L. Hotard & Martin L. Moore & Min Zhao & Zi-Zheng, 2017. "Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein," Nature Communications, Nature, vol. 8(1), pages 1-7, December.
    2. Michael B. Battles & Vicente Más & Eduardo Olmedillas & Olga Cano & Mónica Vázquez & Laura Rodríguez & José A. Melero & Jason S. McLellan, 2017. "Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    3. Anders Krarup & Daphné Truan & Polina Furmanova-Hollenstein & Lies Bogaert & Pascale Bouchier & Ilona J. M. Bisschop & Myra N. Widjojoatmodjo & Roland Zahn & Hanneke Schuitemaker & Jason S. McLellan &, 2015. "A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    4. Davide Corti & Siro Bianchi & Fabrizia Vanzetta & Andrea Minola & Laurent Perez & Gloria Agatic & Barbara Guarino & Chiara Silacci & Jessica Marcandalli & Benjamin J. Marsland & Antonio Piralla & Elen, 2013. "Cross-neutralization of four paramyxoviruses by a human monoclonal antibody," Nature, Nature, vol. 501(7467), pages 439-443, September.
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