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

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. Lim, Florian Krammer, Rong Hai, Peter Palese, Gene S. Tan

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64 Scopus citations


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.

Original languageEnglish
Article number4560
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2018


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