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Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice
Nature (2016) doi:10.1038/nature20564 Received 03 October 2016 Accepted 27 October 2016 Published online 07 November 2016
Abstract
Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease, including congenital birth defects during pregnancy1. To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies (mAbs) from subjects with prior ZIKV infection. A subset of mAbs recognized diverse epitopes on the envelope (E) protein and exhibited potently neutralizing activity. One of the most inhibitory mAbs, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African, Asian, and 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. mAb treatment markedly reduced tissue pathology, placental and fetal infection, and mortality in mice. Thus, neutralizing human mAbs can protect against maternal?fetal transmission, infection and disease, and reveal important determinants for structure-based rational vaccine design efforts.
- Gopal Sapparapu,
- Estefania Fernandez,
- Nurgun Kose,
- 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
Nature (2016) doi:10.1038/nature20564 Received 03 October 2016 Accepted 27 October 2016 Published online 07 November 2016
Abstract
Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease, including congenital birth defects during pregnancy1. To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies (mAbs) from subjects with prior ZIKV infection. A subset of mAbs recognized diverse epitopes on the envelope (E) protein and exhibited potently neutralizing activity. One of the most inhibitory mAbs, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African, Asian, and 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. mAb treatment markedly reduced tissue pathology, placental and fetal infection, and mortality in mice. Thus, neutralizing human mAbs can protect against maternal?fetal transmission, infection and disease, and reveal important determinants for structure-based rational vaccine design efforts.
