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A highly potent human antibody neutralizes dengue virus serotype 3 by binding across three surface proteins

Author

Listed:
  • Guntur Fibriansah

    (Program in Emerging Infectious Diseases, Duke–NUS Graduate Medical School
    Centre for BioImaging Sciences, National University of Singapore)

  • Joanne L. Tan

    (Program in Emerging Infectious Diseases, Duke–NUS Graduate Medical School
    Centre for BioImaging Sciences, National University of Singapore)

  • Scott A. Smith

    (Vanderbilt University
    The Vanderbilt Vaccine Center, Vanderbilt University,Vanderbilt University Medical Center)

  • Ruklanthi de Alwis

    (University of North Carolina at Chapel Hill)

  • Thiam-Seng Ng

    (Program in Emerging Infectious Diseases, Duke–NUS Graduate Medical School
    Centre for BioImaging Sciences, National University of Singapore)

  • Victor A. Kostyuchenko

    (Program in Emerging Infectious Diseases, Duke–NUS Graduate Medical School
    Centre for BioImaging Sciences, National University of Singapore)

  • Ramesh S. Jadi

    (University of North Carolina at Chapel Hill)

  • Petra Kukkaro

    (Program in Emerging Infectious Diseases, Duke–NUS Graduate Medical School
    Centre for BioImaging Sciences, National University of Singapore)

  • Aravinda M. de Silva

    (University of North Carolina at Chapel Hill)

  • James E. Crowe

    (The Vanderbilt Vaccine Center, Vanderbilt University,Vanderbilt University Medical Center
    Microbiology and Immunology, Vanderbilt University, Vanderbilt University Medical Center)

  • Shee-Mei Lok

    (Program in Emerging Infectious Diseases, Duke–NUS Graduate Medical School
    Centre for BioImaging Sciences, National University of Singapore)

Abstract

Dengue virus (DENV) infects ~400 million people annually. There is no licensed vaccine or therapeutic drug. Only a small fraction of the total DENV-specific antibodies in a naturally occurring dengue infection consists of highly neutralizing antibodies. Here we show that the DENV-specific human monoclonal antibody 5J7 is exceptionally potent, neutralizing 50% of virus at nanogram-range antibody concentration. The 9 Å resolution cryo-electron microscopy structure of the Fab 5J7–DENV complex shows that a single Fab molecule binds across three envelope proteins and engages three functionally important domains, each from a different envelope protein. These domains are critical for receptor binding and fusion to the endosomal membrane. The ability to bind to multiple domains allows the antibody to fully coat the virus surface with only 60 copies of Fab, that is, half the amount compared with other potent antibodies. Our study reveals a highly efficient and unusual mechanism of molecular recognition by an antibody.

Suggested Citation

  • Guntur Fibriansah & Joanne L. Tan & Scott A. Smith & Ruklanthi de Alwis & Thiam-Seng Ng & Victor A. Kostyuchenko & Ramesh S. Jadi & Petra Kukkaro & Aravinda M. de Silva & James E. Crowe & Shee-Mei Lok, 2015. "A highly potent human antibody neutralizes dengue virus serotype 3 by binding across three surface proteins," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7341
    DOI: 10.1038/ncomms7341
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    Cited by:

    1. Xin-Ni Lim & Chao Shan & Jan K Marzinek & Hongping Dong & Thiam Seng Ng & Justin S G Ooi & Guntur Fibriansah & Jiaqi Wang & Chandra S Verma & Peter J Bond & Pei-Yong Shi & Shee-mei Lok, 2019. "Molecular basis of dengue virus serotype 2 morphological switch from 29°C to 37°C," PLOS Pathogens, Public Library of Science, vol. 15(9), pages 1-25, September.

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