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Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy

Author

Listed:
  • Alex W. Wessel

    (Washington University School of Medicine)

  • Nurgun Kose

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

  • Robin G. Bombardi

    (Vanderbilt University Medical Center)

  • Vicky Roy

    (Ragon Institute of MGH, MIT, and Harvard University)

  • Warangkana Chantima

    (University of Oxford)

  • Juthathip Mongkolsapaya

    (University of Oxford
    Mahidol University)

  • Melissa A. Edeling

    (Washington University School of Medicine)

  • Christopher A. Nelson

    (Washington University School of Medicine)

  • Irene Bosch

    (E25Bio, Inc., The Engine of MIT)

  • Galit Alter

    (Ragon Institute of MGH, MIT, and Harvard University)

  • Gavin R. Screaton

    (University of Oxford)

  • David H. Fremont

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • James E. Crowe

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

  • Michael S. Diamond

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

Abstract

There are no licensed therapeutics or vaccines available against Zika virus (ZIKV) to counteract its potential for congenital disease. Antibody-based countermeasures targeting the ZIKV envelope protein have been hampered by concerns for cross-reactive responses that induce antibody-dependent enhancement (ADE) of heterologous flavivirus infection. Nonstructural protein 1 (NS1) is a membrane-associated and secreted glycoprotein that functions in flavivirus replication and immune evasion but is absent from the virion. Although some studies suggest that antibodies against ZIKV NS1 are protective, their activity during congenital infection is unknown. Here we develop mouse and human anti-NS1 monoclonal antibodies that protect against ZIKV in both non-pregnant and pregnant mice. Avidity of antibody binding to cell-surface NS1 along with Fc effector functions engagement correlate with protection in vivo. Protective mAbs map to exposed epitopes in the wing domain and loop face of the β-platform. Anti-NS1 antibodies provide an alternative strategy for protection against congenital ZIKV infection without causing ADE.

Suggested Citation

  • Alex W. Wessel & Nurgun Kose & Robin G. Bombardi & Vicky Roy & Warangkana Chantima & Juthathip Mongkolsapaya & Melissa A. Edeling & Christopher A. Nelson & Irene Bosch & Galit Alter & Gavin R. Screato, 2020. "Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19096-y
    DOI: 10.1038/s41467-020-19096-y
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    Cited by:

    1. Xinglong Liu & Zhengfeng Li & Xiaoxia Li & Weixuan Wu & Huadong Jiang & Yufen Zheng & Junjie Zhou & Xianmiao Ye & Junnan Lu & Wei Wang & Lei Yu & Yiping Li & Linbing Qu & Jianhua Wang & Feng Li & Ling, 2024. "A single-dose circular RNA vaccine prevents Zika virus infection without enhancing dengue severity in mice," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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