Structural Basis of Zika Virus-Specific Antibody Protection
Cell July 2016Haiyan Zhao et al.
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.
HYPE-5 Transfection Kit is dedicated to achieve High Yield Protein Expression
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