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Nature. 2016 Dec 15;540(7633):443-447. doi: 10.1038/nature20564. Epub 2016 Nov 7.

Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice.

Author information

1
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
2
The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
3
Department of Pathology &Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
4
Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, Missouri, USA.
5
Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
6
Integral Molecular, Philadelphia, Pennsylvania, USA.
7
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri, USA.
8
Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, Missouri, USA.
9
Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, USA.

Abstract

Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease, including congenital birth defects during pregnancy. To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies from subjects that were previously infected with ZIKV. We show that a subset of antibodies recognize diverse epitopes on the envelope (E) protein and exhibit potent neutralizing activity. One of the most inhibitory antibodies, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African and Asian-American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer-dimer interface. We evaluated the therapeutic efficacy of ZIKV-117 in pregnant and non-pregnant mice. Monoclonal antibody treatment markedly reduced tissue pathology, placental and fetal infection, and mortality in mice. Thus, neutralizing human antibodies can protect against maternal-fetal transmission, infection and disease, and reveal important determinants for structure-based rational vaccine design efforts.

Comment in

PMID:
27819683
PMCID:
PMC5583716
DOI:
10.1038/nature20564
[Indexed for MEDLINE]
Free PMC Article

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