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TitleA Human Bi-specific Antibody against Zika Virus with High Therapeutic Potential.
Journal, issue, pagesCell, Vol. 171, Issue 1, Page 229-241.e15, Year 2017
Publish dateSep 21, 2017
AuthorsJiaqi Wang / Marco Bardelli / Diego A Espinosa / Mattia Pedotti / Thiam-Seng Ng / Siro Bianchi / Luca Simonelli / Elisa X Y Lim / Mathilde Foglierini / Fabrizia Zatta / Stefano Jaconi / Martina Beltramello / Elisabetta Cameroni / Guntur Fibriansah / Jian Shi / Taylor Barca / Isabel Pagani / Alicia Rubio / Vania Broccoli / Elisa Vicenzi / Victoria Graham / Steven Pullan / Stuart Dowall / Roger Hewson / Simon Jurt / Oliver Zerbe / Karin Stettler / Antonio Lanzavecchia / Federica Sallusto / Andrea Cavalli / Eva Harris / Shee-Mei Lok / Luca Varani / Davide Corti /
PubMed AbstractZika 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 ...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.
External linksCell / PubMed:28938115 / PubMed Central
MethodsEM (single particle) / NMR (solution)
Resolution22.0 Å
Structure data

6793

5y0a

EMDB-6793, PDB-5y0a:
Cryo-EM structure of zika virus complexed with Fab of ZKA190 at pH 8.0 and 37 celsius degree
Method: EM (single particle) / Resolution: 22.0 Å

EMDB-6794:
Cryo-EM structure of zika virus complexed with Fab of a human monoclonal antibody named ZKA190 at 4 degrees celsius
Method: EM (single particle) / Resolution: 22.0 Å

PDB-5omz:
Solution structure of domain III (DIII)of Zika virus Envelope protein
Method: SOLUTION NMR

Source
  • Zika virus
  • zika virus (strain mr 766)
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / ZIKA virus Envelope protein domain / ZIKV / VIRUS/IMMUNE SYSTEM / virus / antibody / complex / VIRUS-IMMUNE SYSTEM complex / icosahedral virus

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