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 - Funding Information:
This work was supported by NIH grants R01 AI073755 (to M.S.D. and D.H.F) and R01 AI104972 (to M.S.D.), and NIAID contracts HHSN272201400018C (to D.H.F. and M.S.D) and HHSN272201200026C (CSGID; to D.H.F.). E.F. and D.J.P. were supported by an NIH Pre-doctoral training grant award (T32 AI007163) and the NIH Research Education Program (R25 HG006687), respectively. K.A.D., S.D.S., and T.C.P. were funded by the intramural program of NIAID. We acknowledge Jay Nix (MBC 4.2.2 beamline at ALS Berkeley) for aid in remote data collection. M.S.D. consults for Inbios, Visterra, Sanofi, and Takeda Pharmaceuticals, is on the Scientific Advisory Boards of Moderna and OraGene, and has received research grants from Moderna, Sanofi, and Visterra.
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 -