TY - JOUR
T1 - Structural Basis of Zika Virus-Specific Antibody Protection
AU - Zhao, Haiyan
AU - Fernandez, Estefania
AU - Dowd, Kimberly A.
AU - Speer, Scott D.
AU - Platt, Derek J.
AU - Gorman, Matthew J.
AU - Govero, Jennifer
AU - Nelson, Christopher A.
AU - Pierson, Theodore C.
AU - Diamond, Michael S.
AU - Fremont, Daved H.
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/8/11
Y1 - 2016/8/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84981333003&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2016.07.020
DO - 10.1016/j.cell.2016.07.020
M3 - Article
C2 - 27475895
AN - SCOPUS:84981333003
SN - 0092-8674
VL - 166
SP - 1016
EP - 1027
JO - Cell
JF - Cell
IS - 4
ER -