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Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state

Author

Listed:
  • Iebe Rossey

    (Medical Biotechnology Center
    Ghent University)

  • Morgan S. A. Gilman

    (Geisel School of Medicine at Dartmouth)

  • Stephanie C. Kabeche

    (Geisel School of Medicine at Dartmouth)

  • Koen Sedeyn

    (Medical Biotechnology Center
    Ghent University)

  • Daniel Wrapp

    (Geisel School of Medicine at Dartmouth)

  • Masaru Kanekiyo

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Man Chen

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Vicente Mas

    (Centro Nacional de Microbiología and CIBER de Enfermedades Respiratorias)

  • Jan Spitaels

    (Medical Biotechnology Center
    Ghent University)

  • José A. Melero

    (Centro Nacional de Microbiología and CIBER de Enfermedades Respiratorias)

  • Barney S. Graham

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Bert Schepens

    (Medical Biotechnology Center
    Ghent University)

  • Jason S. McLellan

    (Geisel School of Medicine at Dartmouth)

  • Xavier Saelens

    (Medical Biotechnology Center
    Ghent University)

Abstract

Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV.

Suggested Citation

  • Iebe Rossey & Morgan S. A. Gilman & Stephanie C. Kabeche & Koen Sedeyn & Daniel Wrapp & Masaru Kanekiyo & Man Chen & Vicente Mas & Jan Spitaels & José A. Melero & Barney S. Graham & Bert Schepens & Ja, 2017. "Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state," Nature Communications, Nature, vol. 8(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14158
    DOI: 10.1038/ncomms14158
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    Cited by:

    1. Nicole V. Johnson & Revina C. Scherpenzeel & Mark J. G. Bakkers & Ajit R. Ramamohan & Daan Overveld & Lam Le & Johannes P. M. Langedijk & Joost A. Kolkman & Jason S. McLellan, 2024. "Structural basis for potent neutralization of human respirovirus type 3 by protective single-domain camelid antibodies," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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