Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice

Article

关键词: WEST-NILE-VIRUS;    MONOCLONAL-ANTIBODIES;    CROSS-REACTIVITY;    INFECTION;    PREGNANCY;    ENHANCEMENT;    PROTECTION;    EXPOSURE;   

DOI  :  10.1038/nature20564

来源: SCIE

【 摘 要 】

Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease, including congenital birth defects during pregnancy(1). 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.

【 授权许可】

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