A Human Bi-specific Antibody against Zika Virus with High Therapeutic Potential | Zendy

Jiaqi Wang | Zendy; Marco Bardelli | Zendy; Diego A. Espinosa | Zendy; Mattia Pedotti | Zendy; ThiamSeng Ng | Zendy; Siro Bianchi | Zendy; Luca Simonelli | Zendy; Elisa X. Y. Lim | Zendy; Mathilde Foglierini | Zendy; Fabrizia Zatta | Zendy; Stefano Jaconi | Zendy; Martina Beltramello | Zendy; Elisabetta Cameroni | Zendy; G. Fibriansah | Zendy; Jian Shi | Zendy; Taylor Barca | Zendy; Isabel Pagani | Zendy; Alicia Rubio | Zendy; Vania Broccoli | Zendy; Elisa Vicenzi | Zendy; Victoria Graham | Zendy; Steven T. Pullan | Zendy; Stuart Dowall | Zendy; Roger Hewson | Zendy; Simon Jurt | Zendy; Oliver Zerbe | Zendy; Karin Stettler | Zendy; Antonio Lanzavecchia | Zendy; Federica Sallusto | Zendy; Andrea Cavalli | Zendy; Eva Harris | Zendy; SheeMei Lok | Zendy; Luca Varani | Zendy; Davide Corti | Zendy

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A Human Bi-specific Antibody against Zika Virus with High Therapeutic Potential

Author(s) -

Jiaqi Wang,

Marco Bardelli,

Diego A. Espinosa,

Mattia Pedotti,

ThiamSeng Ng,

Siro Bianchi,

Luca Simonelli,

Elisa X. Y. Lim,

Mathilde Foglierini,

Fabrizia Zatta,

Stefano Jaconi,

Martina Beltramello,

Elisabetta Cameroni,

G. Fibriansah,

Jian Shi,

Taylor Barca,

Isabel Pagani,

Alicia Rubio,

Vania Broccoli,

Elisa Vicenzi,

Victoria Graham,

Steven T. Pullan,

Stuart Dowall,

Roger Hewson,

Simon Jurt,

Oliver Zerbe,

Karin Stettler,

Antonio Lanzavecchia,

Federica Sallusto,

Andrea Cavalli,

Eva Harris,

SheeMei Lok,

Luca Varani,

Davide Corti

Publication year - 2017

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2017.09.002

Subject(s) - biology , virology , zika virus , monoclonal antibody , flavivirus , epitope , in vivo , antibody , in vitro , virus , capsid , immunology , biochemistry , genetics

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

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