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TitleSystematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection.
Journal, issue, pagesCell, Vol. 174, Issue 4, Page 938-952.e13, Year 2018
Publish dateAug 9, 2018
AuthorsErica Ollmann Saphire / Sharon L Schendel / Marnie L Fusco / Karthik Gangavarapu / Bronwyn M Gunn / Anna Z Wec / Peter J Halfmann / Jennifer M Brannan / Andrew S Herbert / Xiangguo Qiu / Kshitij Wagh / Shihua He / Elena E Giorgi / James Theiler / Kathleen B J Pommert / Tyler B Krause / Hannah L Turner / Charles D Murin / Jesper Pallesen / Edgar Davidson / Rafi Ahmed / M Javad Aman / Alexander Bukreyev / Dennis R Burton / James E Crowe / Carl W Davis / George Georgiou / Florian Krammer / Christos A Kyratsous / Jonathan R Lai / Cory Nykiforuk / Michael H Pauly / Pramila Rijal / Ayato Takada / Alain R Townsend / Viktor Volchkov / Laura M Walker / Cheng-I Wang / Larry Zeitlin / Benjamin J Doranz / Andrew B Ward / Bette Korber / Gary P Kobinger / Kristian G Andersen / Yoshihiro Kawaoka / Galit Alter / Kartik Chandran / John M Dye / /
PubMed AbstractAntibodies are promising post-exposure therapies against emerging viruses, but which antibody features and in vitro assays best forecast protection are unclear. Our international consortium ...Antibodies are promising post-exposure therapies against emerging viruses, but which antibody features and in vitro assays best forecast protection are unclear. Our international consortium systematically evaluated antibodies against Ebola virus (EBOV) using multidisciplinary assays. For each antibody, we evaluated epitopes recognized on the viral surface glycoprotein (GP) and secreted glycoprotein (sGP), readouts of multiple neutralization assays, fraction of virions left un-neutralized, glycan structures, phagocytic and natural killer cell functions elicited, and in vivo protection in a mouse challenge model. Neutralization and induction of multiple immune effector functions (IEFs) correlated most strongly with protection. Neutralization predominantly occurred via epitopes maintained on endosomally cleaved GP, whereas maximal IEF mapped to epitopes farthest from the viral membrane. Unexpectedly, sGP cross-reactivity did not significantly influence in vivo protection. This comprehensive dataset provides a rubric to evaluate novel antibodies and vaccine responses and a roadmap for therapeutic development for EBOV and related viruses.
External linksCell / PubMed:30096313 / PubMed Central
MethodsEM (single particle)
Resolution16.0 - 28.0 Å
Structure data

EMDB-7908:
VIC170 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 22.0 Å

EMDB-7909:
VIC169 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 26.0 Å

EMDB-7910:
VIC167 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 19.0 Å

EMDB-7911:
VIC166 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 28.0 Å

EMDB-7912:
VIC165 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 19.0 Å

EMDB-7914:
VIC1164 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-7915:
VIC163 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 19.0 Å

EMDB-7916:
VIC161 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 24.0 Å

EMDB-7917:
VIC160 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 24.0 Å

EMDB-7918:
VIC158 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 24.0 Å

EMDB-7919:
VIC157 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 23.0 Å

EMDB-7920:
VIC142 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 23.0 Å

EMDB-7921:
VIC139 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 22.0 Å

EMDB-7922:
VIC133 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 19.0 Å

EMDB-7923:
VIC101 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 22.0 Å

EMDB-7924:
VIC94 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 22.0 Å

EMDB-7925:
VIC91 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 26.0 Å

EMDB-7926:
VIC82 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 23.0 Å

EMDB-7927:
VIC43 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 22.0 Å

EMDB-7928:
VIC32 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 19.0 Å

EMDB-7929:
VIC26 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 19.0 Å

EMDB-7930:
VIC16 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 26.0 Å

EMDB-7931:
VIC15 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 16.0 Å

EMDB-7932:
VIC12 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 22.0 Å

EMDB-7933:
VIC11 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-7934:
VIC130 Fab in complex with Ebola virus GP
Method: EM (single particle) / Resolution: 26.0 Å

Source
  • Ebola virus - Mayinga, Zaire, 1976

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