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Human antibodies targeting Zika virus NS1 provide protection against disease in a mouse model

Author

Listed:
  • Mark J. Bailey

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • James Duehr

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Harrison Dulin

    (University of California Riverside)

  • Felix Broecker

    (Icahn School of Medicine at Mount Sinai)

  • Julia A. Brown

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Fortuna O. Arumemi

    (The J. Craig Venter Institute)

  • Maria C. Bermúdez González

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Victor H. Leyva-Grado

    (Icahn School of Medicine at Mount Sinai)

  • Matthew J. Evans

    (Icahn School of Medicine at Mount Sinai)

  • Viviana Simon

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Jean K. Lim

    (Icahn School of Medicine at Mount Sinai)

  • Florian Krammer

    (Icahn School of Medicine at Mount Sinai)

  • Rong Hai

    (University of California Riverside)

  • Peter Palese

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Gene S. Tan

    (The J. Craig Venter Institute
    University of California San Diego)

Abstract

Zika virus is a mosquito-borne flavivirus closely related to dengue virus that can cause severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Specific treatments and vaccines for Zika virus are not currently available. Here, we isolate and characterize four monoclonal antibodies (mAbs) from an infected patient that target the non-structural protein NS1. We show that while these antibodies are non-neutralizing, NS1-specific mAbs can engage FcγR without inducing antibody dependent enhancement (ADE) of infection in vitro. Moreover, we demonstrate that mAb AA12 has protective efficacy against lethal challenges of African and Asian lineage strains of Zika virus in Stat2–/– mice. Protection is Fc-dependent, as a mutated antibody unable to activate known Fc effector functions or complement is not protective in vivo. This study highlights the importance of the ZIKV NS1 protein as a potential vaccine antigen.

Suggested Citation

  • Mark J. Bailey & James Duehr & Harrison Dulin & Felix Broecker & Julia A. Brown & Fortuna O. Arumemi & Maria C. Bermúdez González & Victor H. Leyva-Grado & Matthew J. Evans & Viviana Simon & Jean K. L, 2018. "Human antibodies targeting Zika virus NS1 provide protection against disease in a mouse model," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07008-0
    DOI: 10.1038/s41467-018-07008-0
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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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