TY - JOUR
T1 - Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection
AU - Fernandez, Estefania
AU - Dejnirattisai, Wanwisa
AU - Cao, Bin
AU - Scheaffer, Suzanne M.
AU - Supasa, Piyada
AU - Wongwiwat, Wiyada
AU - Esakky, Prabagaran
AU - Drury, Andrea
AU - Mongkolsapaya, Juthathip
AU - Moley, Kelle H.
AU - Mysorekar, Indira U.
AU - Screaton, Gavin R.
AU - Diamond, Michael S.
N1 - Funding Information:
We thank Haina Shin for advice on the intravaginal infection experiments, S. Whitehead (US National Institutes of Health (NIH)) for ZIKV-Brazil (Paraiba, 2015), S. Shresta(La Jolla Institute of Allergy and Immunology) for DENV-2 strain D2S20, P. Malasit and S. Noisakran (Mahidol University) for DENV-1, DENV-3, and DENV-4 isolates from patients, C. Simmons (University of Melbourne) for DENV-2 strain DF-699, A. Kohl, R.F. de Oliveira Freitas, and L.J. Pena (University of Glasgow) for ZIKV-Brazil PE243, and A. Sakuntabhai (Institut Pasteur) for ZIKV-Africa HD78788. Supported by grants and contracts from the NIH (R01 AI073755 (M.S.D.), R01 AI127828 (M.S.D.), R01 HD091218 (I.U.M. and M.S.D.), HHSN272201400018C (M.S.D.), T32 AI007163 (E.F.)), the Wellcome Trust (G.R.S.), MRC-NEWTON UK (J.M.), and the National Institute for Health Research Biomedical Research Centre funding scheme UK (G.R.S.).
Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
PY - 2017/10/18
Y1 - 2017/10/18
N2 - The Zika virus (ZIKV) epidemic has resulted in congenital abnormalities in fetuses and neonates. Although some cross-reactive dengue virus (DENV)-specific antibodies can enhance ZIKV infection in mice, those recognizing the DENV E-dimer epitope (EDE) can neutralize ZIKV infection in cell culture. We evaluated the therapeutic activity of human monoclonal antibodies to DENV EDE for their ability to control ZIKV infection in the brains, testes, placentas, and fetuses of mice. A single dose of the EDE1-B10 antibody given 3 d after ZIKV infection protected against lethality, reduced ZIKV levels in brains and testes, and preserved sperm counts. In pregnant mice, wild-type or engineered LALA variants of EDE1-B10, which cannot engage Fcg receptors, diminished ZIKV burden in maternal and fetal tissues, and protected against fetal demise. Because neutralizing antibodies to EDE have therapeutic potential against ZIKV, in addition to their established inhibitory effects against DENV, it may be possible to develop therapies that control disease caused by both viruses.
AB - The Zika virus (ZIKV) epidemic has resulted in congenital abnormalities in fetuses and neonates. Although some cross-reactive dengue virus (DENV)-specific antibodies can enhance ZIKV infection in mice, those recognizing the DENV E-dimer epitope (EDE) can neutralize ZIKV infection in cell culture. We evaluated the therapeutic activity of human monoclonal antibodies to DENV EDE for their ability to control ZIKV infection in the brains, testes, placentas, and fetuses of mice. A single dose of the EDE1-B10 antibody given 3 d after ZIKV infection protected against lethality, reduced ZIKV levels in brains and testes, and preserved sperm counts. In pregnant mice, wild-type or engineered LALA variants of EDE1-B10, which cannot engage Fcg receptors, diminished ZIKV burden in maternal and fetal tissues, and protected against fetal demise. Because neutralizing antibodies to EDE have therapeutic potential against ZIKV, in addition to their established inhibitory effects against DENV, it may be possible to develop therapies that control disease caused by both viruses.
UR - http://www.scopus.com/inward/record.url?scp=85031797326&partnerID=8YFLogxK
U2 - 10.1038/ni.3849
DO - 10.1038/ni.3849
M3 - Article
C2 - 28945244
AN - SCOPUS:85031797326
VL - 18
SP - 1261
EP - 1269
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 11
ER -