EMD-7900

Single-particle
23.0 Å
EMD-7900 Deposition: 23/05/2018
Map released: 13/06/2018
Last modified: 12/12/2018
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-7900

REGN3479 antibody Fab in complex with Ebola virus GP

EMD-7900

Single-particle
23.0 Å
EMD-7900 Deposition: 23/05/2018
Map released: 13/06/2018
Last modified: 12/12/2018
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Ebola virus - Mayinga, Zaire, 1976
Sample: REGN3479 antibody Fab in complex with Ebola virus GP

Deposition Authors: Turner H, Murin CD, Ward AB
Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates.
PUBMED: 29860496
DOI: doi:10.1093/infdis/jiy285
ISSN: 1537-6613
Abstract:
Background
For most classes of drugs, rapid development of therapeutics to treat emerging infections is challenged by the timelines needed to identify compounds with the desired efficacy, safety, and pharmacokinetic profiles. Fully human monoclonal antibodies (mAbs) provide an attractive method to overcome many of these hurdles to rapidly produce therapeutics for emerging diseases.
Methods
In this study, we deployed a platform to generate, test, and develop fully human antibodies to Zaire ebolavirus. We obtained specific anti-Ebola virus (EBOV) antibodies by immunizing VelocImmune mice that use human immunoglobulin variable regions in their humoral responses.
Results
Of the antibody clones isolated, 3 were selected as best at neutralizing EBOV and triggering FcγRIIIa. Binding studies and negative-stain electron microscopy revealed that the 3 selected antibodies bind to non-overlapping epitopes, including a potentially new protective epitope not targeted by other antibody-based treatments. When combined, a single dose of a cocktail of the 3 antibodies protected nonhuman primates (NHPs) from EBOV disease even after disease symptoms were apparent.
Conclusions
This antibody cocktail provides complementary mechanisms of actions, incorporates novel specificities, and demonstrates high-level postexposure protection from lethal EBOV disease in NHPs. It is now undergoing testing in normal healthy volunteers in preparation for potential use in future Ebola epidemics.