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

Gopal Sapparapu, Estefania Fernandez, Nurgun Kose, Cao Bin Cao, Julie M. Fox, Robin G. Bombardi, Haiyan Zhao, Christopher A. Nelson, Aubrey L. Bryan, Trevor Barnes, Edgar Davidson, Indira U. Mysorekar, Daved H. Fremont, Benjamin J. Doranz, Michael S. Diamond, James E. Crowe

Research output: Contribution to journalArticlepeer-review

275 Scopus citations

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.

Original languageEnglish
Pages (from-to)443-447
Number of pages5
JournalNature
Volume540
Issue number7633
DOIs
StatePublished - Dec 15 2016

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