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Structural Basis of Zika Virus-Specific Antibody Protection
Haiyan Zhao7
, Estefania Fernandez7
, Kimberly A. Dowd
, Scott D. Speer
, Derek J. Platt
, Matthew J. Gorman
, Jennifer Govero
, Christopher A. Nelson
, Theodore C. Pierson
, Michael S. Diamond
Press enter key for correspondence information
Press enter key to Email the author
, Daved H. FremontPress enter key for correspondence informationPress enter key to Email the author
7Co-first author
Publication stage: In Press Corrected Proof
DOI: http://dx.doi.org/10.1016/j.cell.2016.07.020
Article Info
Highlights
Summary
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.
full article
Haiyan Zhao7
, Estefania Fernandez7
, Kimberly A. Dowd
, Scott D. Speer
, Derek J. Platt
, Matthew J. Gorman
, Jennifer Govero
, Christopher A. Nelson
, Theodore C. Pierson
, Michael S. Diamond
Press enter key for correspondence informationPress enter key to Email the author, Daved H. Fremont
Press enter key for correspondence informationPress enter key to Email the author7Co-first author
Publication stage: In Press Corrected Proof
DOI: http://dx.doi.org/10.1016/j.cell.2016.07.020
Article InfoHighlights
- ?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
Summary
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.
full article
