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Title: Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection
Authors: Estefania Fernandez
Wanwisa Dejnirattisai
Bin Cao
Suzanne M. Scheaffer
Piyada Supasa
Wiyada Wongwiwat
Prabagaran Esakky
Andrea Drury
Juthathip Mongkolsapaya
Kelle H. Moley
Indira U. Mysorekar
Gavin R. Screaton
Michael S. Diamond
Washington University School of Medicine in St. Louis
Imperial College London
Mahidol University
University of Oxford
Keywords: Immunology and Microbiology
Issue Date: 18-Oct-2017
Citation: Nature Immunology. Vol.18, No.11 (2017), 1261-1269
Abstract: © 2017 Nature America, Inc., part of Springer Nature. All rights reserved. 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.
ISSN: 15292916
Appears in Collections:Scopus 2016-2017

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