EMD-7910
VIC167 Fab in complex with Ebola virus GP
EMD-7910
Single-particle19.0 Å

Map released: 25/07/2018
Last modified: 22/08/2018
Sample Organism:
Ebola virus - Mayinga, Zaire, 1976
Sample: Complex of VIC167 Fab bound to Ebola virus GP
Deposition Authors: Turner H, Murin CD, Pallesen J, Ward AB
Sample: Complex of VIC167 Fab bound to Ebola virus GP
Deposition Authors: Turner H, Murin CD, Pallesen J, Ward AB
Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection.
Saphire EO,
Schendel SL
,
Fusco ML,
Gangavarapu K,
Gunn BM
,
Wec AZ,
Halfmann PJ,
Brannan JM,
Herbert AS,
Qiu X,
Wagh K,
He S,
Giorgi EE,
Theiler J,
Pommert KBJ,
Krause TB,
Turner HL,
Murin CD,
Pallesen J
,
Davidson E,
Ahmed R,
Aman MJ,
Bukreyev A,
Burton DR,
Crowe Jr. JE
,
Davis CW
,
Georgiou G,
Krammer F,
Kyratsous CA,
Lai JR,
Nykiforuk C,
Pauly MH,
Rijal P
,
Takada A,
Townsend AR,
Volchkov V
,
Walker LM,
Wang CI,
Zeitlin L,
Doranz BJ,
Ward AB,
Korber B,
Kobinger GP,
Andersen KG
,
Kawaoka Y,
Alter G,
Chandran K,
Dye JM
(2018) Cell , 174 , 938 - 952.e13









(2018) Cell , 174 , 938 - 952.e13
Abstract:
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.
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.