Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Africa
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Americas
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Animals
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Antibodies, Monoclonal / chemistry
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / therapeutic use
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Antibodies, Neutralizing / chemistry
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Antibodies, Neutralizing / immunology*
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Antibodies, Neutralizing / therapeutic use
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Antibodies, Viral / chemistry
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Antibodies, Viral / immunology
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Antibodies, Viral / therapeutic use
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Antibody Specificity
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Asia
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B-Lymphocytes / immunology
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Disease Models, Animal
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Epitope Mapping
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Female
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Fetal Diseases / immunology
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Fetal Diseases / prevention & control*
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Fetal Diseases / virology
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Fetus / immunology
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Fetus / virology
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Humans
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Infectious Disease Transmission, Vertical / prevention & control*
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Male
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Mice
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Models, Molecular
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Placenta / immunology
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Placenta / virology
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Pregnancy
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Protein Multimerization
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Survival Rate
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Viral Proteins / chemistry
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Viral Proteins / immunology
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Viral Vaccines / chemistry
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Viral Vaccines / immunology
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Virus Replication / immunology*
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Zika Virus / growth & development*
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Zika Virus / immunology*
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Zika Virus Infection / immunology*
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Zika Virus Infection / pathology
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Zika Virus Infection / virology*
Substances
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Antibodies, Monoclonal
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Antibodies, Neutralizing
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Antibodies, Viral
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Viral Proteins
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Viral Vaccines