TY - JOUR
T1 - Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice
AU - Sapparapu, Gopal
AU - Fernandez, Estefania
AU - Kose, Nurgun
AU - Bin Cao, Cao
AU - Fox, Julie M.
AU - Bombardi, Robin G.
AU - Zhao, Haiyan
AU - Nelson, Christopher A.
AU - Bryan, Aubrey L.
AU - Barnes, Trevor
AU - Davidson, Edgar
AU - Mysorekar, Indira U.
AU - Fremont, Daved H.
AU - Doranz, Benjamin J.
AU - Diamond, Michael S.
AU - Crowe, James E.
N1 - Funding Information:
This work was supported by US N.I.H. grants R01 AI073755 (to M.S.D., D.H.F and J.E.C.), R01 AI104972 (to M.S.D.), US N.I.H. contracts HHSN272201400024C (to J.E.C.), HHSN272201400058C (to B.J.D.), HHSN272201400018C (to D.H.F, M.S.D, and J.E.C) and HHSN272201200026C (CSGID; to D.H.F), and by a Preventing Prematurity Initiative grant from the Burroughs Wellcome Fund and an Investigator award from the March of Dimes (to I.U.M.). E.F. was supported by an N.I.H. Pre-doctoral training grant award (T32 AI007163)
Publisher Copyright:
© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
PY - 2016/12/15
Y1 - 2016/12/15
N2 - Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease, including congenital birth defects during pregnancy. To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies from subjects that were previously infected with ZIKV. We show that a subset of antibodies recognize diverse epitopes on the envelope (E) protein and exhibit potent neutralizing activity. One of the most inhibitory antibodies, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African and Asian-American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer-dimer interface. We evaluated the therapeutic efficacy of ZIKV-117 in pregnant and non-pregnant mice. Monoclonal antibody treatment markedly reduced tissue pathology, placental and fetal infection, and mortality in mice. Thus, neutralizing human antibodies can protect against maternal-fetal transmission, infection and disease, and reveal important determinants for structure-based rational vaccine design efforts.
AB - Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease, including congenital birth defects during pregnancy. To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies from subjects that were previously infected with ZIKV. We show that a subset of antibodies recognize diverse epitopes on the envelope (E) protein and exhibit potent neutralizing activity. One of the most inhibitory antibodies, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African and Asian-American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer-dimer interface. We evaluated the therapeutic efficacy of ZIKV-117 in pregnant and non-pregnant mice. Monoclonal antibody treatment markedly reduced tissue pathology, placental and fetal infection, and mortality in mice. Thus, neutralizing human antibodies can protect against maternal-fetal transmission, infection and disease, and reveal important determinants for structure-based rational vaccine design efforts.
UR - http://www.scopus.com/inward/record.url?scp=84997533781&partnerID=8YFLogxK
U2 - 10.1038/nature20564
DO - 10.1038/nature20564
M3 - Article
C2 - 27819683
AN - SCOPUS:84997533781
SN - 0028-0836
VL - 540
SP - 443
EP - 447
JO - Nature
JF - Nature
IS - 7633
ER -