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Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection.
- Source :
-
Cell [Cell] 2018 Aug 09; Vol. 174 (4), pp. 938-952.e13. - Publication Year :
- 2018
-
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.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antibodies, Monoclonal administration & dosage
Female
Hemorrhagic Fever, Ebola immunology
Hemorrhagic Fever, Ebola virology
Immunization
Mice
Mice, Inbred BALB C
Treatment Outcome
Antibodies, Monoclonal immunology
Antibodies, Monoclonal isolation & purification
Ebolavirus immunology
Epitopes immunology
Hemorrhagic Fever, Ebola prevention & control
Membrane Glycoproteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 174
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 30096313
- Full Text :
- https://doi.org/10.1016/j.cell.2018.07.033