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Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein

Author

Listed:
  • Daiyin Tian

    (National Institutes of Health
    Children’s Hospital of Chongqing Medical University)

  • Michael B. Battles

    (Geisel School of Medicine at Dartmouth)

  • Syed M. Moin

    (National Institutes of Health)

  • Man Chen

    (National Institutes of Health)

  • Kayvon Modjarrad

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation)

  • Azad Kumar

    (National Institutes of Health)

  • Masaru Kanekiyo

    (National Institutes of Health)

  • Kevin W. Graepel

    (Vanderbilt University Medical Center)

  • Noor M. Taher

    (Geisel School of Medicine at Dartmouth)

  • Anne L. Hotard

    (Emory University
    Division of Select Agents and Toxins, Centers for Disease Control and Prevention)

  • Martin L. Moore

    (Emory University
    Meissa Vaccines, Inc South)

  • Min Zhao

    (School of Public Health, Xiamen University
    Xiamen University)

  • Zi-Zheng Zheng

    (School of Public Health, Xiamen University
    Xiamen University)

  • Ning-Shao Xia

    (School of Public Health, Xiamen University
    Xiamen University)

  • Jason S. McLellan

    (Geisel School of Medicine at Dartmouth)

  • Barney S. Graham

    (National Institutes of Health)

Abstract

A licensed vaccine for respiratory syncytial virus (RSV) is unavailable, and passive prophylaxis with the antibody palivizumab is restricted to high-risk infants. Recently isolated antibodies 5C4 and D25 are substantially more potent than palivizumab, and a derivative of D25 is in clinical trials. Here we show that unlike D25, 5C4 preferentially neutralizes subtype A viruses. The crystal structure of 5C4 bound to the RSV fusion (F) protein reveals that the overall binding mode of 5C4 is similar to that of D25, but their angles of approach are substantially different. Mutagenesis and virological studies demonstrate that RSV F residue 201 is largely responsible for the subtype specificity of 5C4. These results improve our understanding of subtype-specific immunity and the neutralization breadth requirements of next-generation antibodies, and thereby contribute to the design of broadly protective RSV vaccines.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01858-w
    DOI: 10.1038/s41467-017-01858-w
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    Cited by:

    1. Rineke Jong & Norbert Stockhofe-Zurwieden & Judith Bonsing & Kai-Fen Wang & Sarah Vandepaer & Badiaa Bouzya & Jean-François Toussaint & Ilse Dieussaert & Haifeng Song & Ann-Muriel Steff, 2022. "ChAd155-RSV vaccine is immunogenic and efficacious against bovine RSV infection-induced disease in young calves," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Karen J. Gonzalez & Jiachen Huang & Miria F. Criado & Avik Banerjee & Stephen M. Tompkins & Jarrod J. Mousa & Eva-Maria Strauch, 2024. "A general computational design strategy for stabilizing viral class I fusion proteins," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Bryan S. Sibert & Joseph Y. Kim & Jie E. Yang & Zunlong Ke & Christopher C. Stobart & Martin L. Moore & Elizabeth R. Wright, 2024. "Assembly of respiratory syncytial virus matrix protein lattice and its coordination with fusion glycoprotein trimers," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Fabian Sesterhenn & Che Yang & Jaume Bonet & Johannes T. Cramer & Xiaolin Wen & Yimeng Wang & Chi I. Chiang & Luciano Andres Abriata & Iga Kucharska & Giacomo Castoro & Sabrina S. Vollers & Marie Gall, 2020. "De novo protein design enables the precise induction of RSV-neutralizing antibodies," Post-Print hal-02677103, HAL.
    5. 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.

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