Structural Basis of Zika Virus-Specific Antibody Protection

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

Research output: Contribution to journalArticlepeer-review

247 Scopus citations

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.

Original languageEnglish
Pages (from-to)1016-1027
Number of pages12
JournalCell
Volume166
Issue number4
DOIs
StatePublished - Aug 11 2016

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