Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice.
Nature
; 540(7633): 443-447, 2016 12 15.
Article
em En
| MEDLINE
| ID: mdl-27819683
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Replicação Viral
/
Transmissão Vertical de Doenças Infecciosas
/
Anticorpos Neutralizantes
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Doenças Fetais
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Zika virus
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Infecção por Zika virus
País/Região como assunto:
Africa
/
Asia
Idioma:
En
Revista:
Nature
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos