Structural Basis of Zika Virus-Specific Antibody Protection

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2016 Aug 1

PMID 27475895

Citations 227

Authors

Haiyan Zhao

Estefania Fernandez

Kimberly A Dowd

Scott D Speer

Derek J Platt

Matthew J Gorman

Jennifer Govero

Christopher A Nelson

Theodore C Pierson

Michael S Diamond

Daved H Fremont

Affiliations

Soon will be listed here.

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.

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