Details

Autor(en) / Beteiligte

• Zhao, Haiyan
• Fernandez, Estefania
• Dowd, Kimberly A.
• Speer, Scott D.
• Platt, Derek J.
• Gorman, Matthew J.
• Govero, Jennifer
• Nelson, Christopher A.
• Pierson, Theodore C.
• Diamond, Michael S.
• Fremont, Daved H.

Titel

Structural Basis of Zika Virus-Specific Antibody Protection

Ist Teil von

• Cell, 2016-08, Vol.166 (4), p.1016-1027

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •New ZIKV-specific monoclonal antibodies are identified•Three distinct epitopes on E protein DIII are defined by X-ray crystallography•DIII lateral ridge antibodies broadly neutralize ZIKV infection and protect in mice A panel of Zika virus-specific monoclonal antibodies are developed that can neutralize infection of the African, Asian, and American strains. Of these, antibodies that target the lateral ridge epitope in the DIII region of the viral E protein can confer in vivo protection in an animal model of infection and may represent a path for development of prophylactic or therapeutic antibodies in pregnancy or vaccines against Zika virus.