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Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection

by Fernandez, Estefania , Scheaffer, Suzanne M , Moley, Kelle H , Supasa, Piyada , Drury, Andrea , Wongwiwat, Wiyada , Dejnirattisai, Wanwisa , Screaton, Gavin R , Cao, Bin , Mysorekar, Indira U , Diamond, Michael S , Esakky, Prabagaran , Mongkolsapaya, Juthathip

in 13 / 13/1 / 631/250/255/2514 / 631/326/596 / 64 / 64/60 / Animals / Antibodies / Antibodies, Monoclonal - immunology / Antibodies, Viral - immunology / Antigenic determinants / Biomedicine / Brain - immunology / Brain - virology / Brazil / Care and treatment / Cell culture / Chlorocebus aethiops / Cross Reactions - immunology / Dengue fever / Dengue virus / Dengue Virus - classification / Dengue Virus - immunology / Dengue Virus - metabolism / Development and progression / Diagnosis / Diseases / Dosage and administration / Epidemics / Epitopes / Epitopes - immunology / Female / Fetus - immunology / Fetus - virology / Fetuses / Flavivirus / Genetic disorders / Host-Pathogen Interactions - immunology / Humans / Immunoglobulins / Immunology / Infection / Infection control / Infections / Infectious Diseases / Lethality / Male / Medical schools / Mice / Monoclonal antibodies / Neonates / Neutralization Tests / Newborn infants / Pregnancy / Pregnant women / Protein Multimerization - immunology / Sperm / Testis - immunology / Testis - virology / Vector-borne diseases / Vero Cells / Viral Envelope Proteins - chemistry / Viral Envelope Proteins - immunology / Viral Load - immunology / Zika virus / Zika Virus - immunology / Zika Virus - physiology / Zika virus infection / Zika Virus Infection - immunology / Zika Virus Infection - virology

2017

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Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection

2017

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Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection

2017

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Journal Article

Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection

Fernandez, Estefania,

Scheaffer, Suzanne M,

Moley, Kelle H,

Supasa, Piyada,

Drury, Andrea,

Wongwiwat, Wiyada,

Dejnirattisai, Wanwisa,

Screaton, Gavin R,

Cao, Bin,

Mysorekar, Indira U,

Diamond, Michael S,

Esakky, Prabagaran,

Mongkolsapaya, Juthathip

2017

Overview

Diamond, Screaton and colleagues show that certain cross-reactive neutralizing antibodies to dengue virus have therapeutic activity against Zika virus infection in immune-privileged sites in vivo . 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.

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Publisher

Nature Publishing Group US,Nature Publishing Group

Subject

/ 13/1

/ 631/250/255/2514

/ 631/326/596

/ 64

/ 64/60

/ Animals

/ Antibodies