| Literature DB >> 28938115 |
Jiaqi Wang1, Marco Bardelli2, Diego A Espinosa3, Mattia Pedotti2, Thiam-Seng Ng1, Siro Bianchi4, Luca Simonelli2, Elisa X Y Lim1, Mathilde Foglierini2, Fabrizia Zatta4, Stefano Jaconi4, Martina Beltramello4, Elisabetta Cameroni4, Guntur Fibriansah1, Jian Shi5, Taylor Barca3, Isabel Pagani6, Alicia Rubio6, Vania Broccoli7, Elisa Vicenzi6, Victoria Graham8, Steven Pullan8, Stuart Dowall8, Roger Hewson8, Simon Jurt9, Oliver Zerbe9, Karin Stettler4, Antonio Lanzavecchia2, Federica Sallusto2, Andrea Cavalli2, Eva Harris3, Shee-Mei Lok10, Luca Varani11, Davide Corti12.
Abstract
Zika virus (ZIKV), a mosquito-borne flavivirus, causes devastating congenital birth defects. We isolated a human monoclonal antibody (mAb), ZKA190, that potently cross-neutralizes multi-lineage ZIKV strains. ZKA190 is highly effective in vivo in preventing morbidity and mortality of ZIKV-infected mice. NMR and cryo-electron microscopy show its binding to an exposed epitope on DIII of the E protein. ZKA190 Fab binds all 180 E protein copies, altering the virus quaternary arrangement and surface curvature. However, ZIKV escape mutants emerged in vitro and in vivo in the presence of ZKA190, as well as of other neutralizing mAbs. To counter this problem, we developed a bispecific antibody (FIT-1) comprising ZKA190 and a second mAb specific for DII of E protein. In addition to retaining high in vitro and in vivo potencies, FIT-1 robustly prevented viral escape, warranting its development as a ZIKV immunotherapy. CrownEntities:
Keywords: Zika; neutralizing antibody; serotherapy
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Year: 2017 PMID： 28938115 PMCID： PMC5673489 DOI： 10.1016/j.cell.2017.09.002
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582