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Cell. 2016 Aug 11;166(4):1016-1027. doi: 10.1016/j.cell.2016.07.020. Epub 2016 Jul 27.

Structural Basis of Zika Virus-Specific Antibody Protection.

Author information

1
Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
2
Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
3
Viral Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
4
Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA.
5
Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA; The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: diamond@borcim.wustl.edu.
6
Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, Saint Louis, MO 63110, USA; The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: fremont@wustl.edu.

Abstract

Zika virus (ZIKV) infection during pregnancy has emerged as a global public health problem because of its ability to cause severe congenital disease. Here, we developed six mouse monoclonal antibodies (mAbs) against ZIKV including four (ZV-48, ZV-54, ZV-64, and ZV-67) that were ZIKV specific and neutralized infection of African, Asian, and American strains to varying degrees. X-ray crystallographic and competition binding analyses of Fab fragments and scFvs defined three spatially distinct epitopes in DIII of the envelope protein corresponding to the lateral ridge (ZV-54 and ZV-67), C-C' loop (ZV-48 and ZV-64), and ABDE sheet (ZV-2) regions. In vivo passive transfer studies revealed protective activity of DIII-lateral ridge specific neutralizing mAbs in a mouse model of ZIKV infection. Our results suggest that DIII is targeted by multiple type-specific antibodies with distinct neutralizing activity, which provides a path for developing prophylactic antibodies for use in pregnancy or designing epitope-specific vaccines against ZIKV.

PMID:
27475895
PMCID:
PMC4983199
DOI:
10.1016/j.cell.2016.07.020
[Indexed for MEDLINE]
Free PMC Article

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