Structural basis for broad neutralization of ebolaviruses by an antibody targeting the glycoprotein fusion loop
PublisherNature Publishing Group
MetadataShow full item record
AbstractThe severity of the 2014–2016 ebolavirus outbreak in West Africa expedited clinical development of therapeutics and vaccines though the countermeasures on hand were largely monospecific and lacked efficacy against other ebolavirus species that previously emerged. Recent studies indicate that ebolavirus glycoprotein (GP) fusion loops are targets for cross-protective antibodies. Here we report the 3.72 Å resolution crystal structure of one such cross-protective antibody, CA45, bound to the ectodomain of Ebola virus (EBOV) GP. The CA45 epitope spans multiple faces of the fusion loop stem, across both GP1 and GP2 subunits, with ~68% of residues identical across > 99.5% of known ebolavirus isolates. Extensive antibody interactions within a pan-ebolavirus small-molecule inhibitor binding cavity on GP define this cavity as a novel site of immune vulnerability. The structure elucidates broad ebolavirus neutralization through a highly conserved epitope on GP and further enables rational design and development of broadly protective vaccines and therapeutics. Copyright 2018, The Author(s).
SponsorsThis work was supported by an Intramural Research Award from the University of Maryland and by MPower funds from the State of Maryland, the Advanced Photon Source, Argonne National Laboratory, the U.S. Department of Energy, Office of Basic Energy Sciences, under Contract Number W-31-109-Eng-38 and NIAID/NIH grant R01AI126587.
Keywordglycoprotein fusion loop
Hemorrhagic Fever, Ebola--prevention & control
Viral Fusion Proteins
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85054081877&doi=10.1038%2fs41467-018-06113-4&partnerID=40&md5=7d63ab65dd52d6b6e8acd47feeaccfae; http://hdl.handle.net/10713/9401
- Structural Basis of Pan-Ebolavirus Neutralization by a Human Antibody against a Conserved, yet Cryptic Epitope.
- Authors: West BR, Moyer CL, King LB, Fusco ML, Milligan JC, Hui S, Saphire EO
- Issue date: 2018 Sep 11
- Antibody-Mediated Protective Mechanisms Induced by a Trivalent Parainfluenza Virus-Vectored Ebolavirus Vaccine.
- Authors: Kimble JB, Malherbe DC, Meyer M, Gunn BM, Karim MM, Ilinykh PA, Iampietro M, Mohamed KS, Negi S, Gilchuk P, Huang K, Wolf YI, Braun W, Crowe JE, Alter G, Bukreyev A
- Issue date: 2019 Feb 15
- Mapping of Ebolavirus Neutralization by Monoclonal Antibodies in the ZMapp Cocktail Using Cryo-Electron Tomography and Studies of Cellular Entry.
- Authors: Tran EE, Nelson EA, Bonagiri P, Simmons JA, Shoemaker CJ, Schmaljohn CS, Kobinger GP, Zeitlin L, Subramaniam S, White JM
- Issue date: 2016 Sep 1
- Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses.
- Authors: Wec AZ, Herbert AS, Murin CD, Nyakatura EK, Abelson DM, Fels JM, He S, James RM, de La Vega MA, Zhu W, Bakken RR, Goodwin E, Turner HL, Jangra RK, Zeitlin L, Qiu X, Lai JR, Walker LM, Ward AB, Dye JM, Chandran K, Bornholdt ZA
- Issue date: 2017 May 18
- Structural basis for differential neutralization of ebolaviruses.
- Authors: Bale S, Dias JM, Fusco ML, Hashiguchi T, Wong AC, Liu T, Keuhne AI, Li S, Woods VL Jr, Chandran K, Dye JM, Saphire EO
- Issue date: 2012 Apr