Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein

Immunity
Pavlo GilchukJames E Crowe

Abstract

Ebolaviruses cause severe disease in humans, and identification of monoclonal antibodies (mAbs) that are effective against multiple ebolaviruses are important for therapeutics development. Here we describe a distinct class of broadly neutralizing human mAbs with protective capacity against three ebolaviruses infectious for humans: Ebola (EBOV), Sudan (SUDV), and Bundibugyo (BDBV) viruses. We isolated mAbs from human survivors of ebolavirus disease and identified a potent mAb, EBOV-520, which bound to an epitope in the glycoprotein (GP) base region. EBOV-520 efficiently neutralized EBOV, BDBV, and SUDV and also showed protective capacity in relevant animal models of these infections. EBOV-520 mediated protection principally by direct virus neutralization and exhibited multifunctional properties. This study identified a potent naturally occurring mAb and defined key features of the human antibody response that may contribute to broad protection. This multifunctional mAb and related clones are promising candidates for development as broadly protective pan-ebolavirus therapeutic molecules.

References

Sep 5, 1998·The Journal of Infectious Diseases·M BrayJ Huggins
Mar 21, 2001·Molecular Immunology·G R McLeanN S Green
Apr 16, 2005·Science·Kartik ChandranJames M Cunningham
Sep 18, 2007·Science·Marijn van der Neut KolfschotenPaul W H I Parren
Jun 3, 2008·Journal of Immunological Methods·Xiaocong YuJames E Crowe
Nov 22, 2008·PLoS Pathogens·Jonathan S TownerStuart T Nichol
Mar 6, 2009·Journal of Structural Biology·Gabriel C LanderBridget Carragher
Jan 1, 2009·Future Virology·Jeffrey E Lee, Erica Ollmann Saphire
Aug 26, 2011·Nature·Jan E CaretteThijn R Brummelkamp
Oct 19, 2011·The Journal of Infectious Diseases·JoLynne RaymondMike Bray
Sep 25, 2012·Journal of Structural Biology·Sjors H W Scheres
May 24, 2014·Immunology·Edgar Davidson, Benjamin J Doranz
Aug 30, 2014·Nature·Xiangguo QiuGary P Kobinger
Nov 19, 2014·Proceedings of the National Academy of Sciences of the United States of America·Charles D MurinErica Ollmann Saphire
Feb 28, 2015·Cell·Andrew I FlyakJames E Crowe
Mar 12, 2015·Current Opinion in HIV and AIDS·Constantinos Kurt WibmerLynn Morris
Aug 28, 2015·Journal of Virology·Edgar DavidsonBenjamin J Doranz
Oct 23, 2015·Journal of Virology·Gary WongXiangguo Qiu
Jan 29, 2016·Journal of Virology·Philipp A IlinykhAlexander Bukreyev
Feb 11, 2016·MBio·Jennifer S SpenceKartik Chandran
Mar 8, 2016·The Journal of Clinical Investigation·Natalie J ThornburgJames E Crowe
Jun 25, 2016·Trends in Microbiology·Erica Ollmann Saphire, M Javad Aman
Aug 27, 2016·Nature Microbiology·Jesper PallesenAndrew B Ward
Oct 13, 2016·The New England Journal of Medicine·UNKNOWN PREVAIL II Writing GroupDenis Malvy
Apr 12, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Cordelia E M ColtartDavid L Heymann
Apr 14, 2017·Cell Reports·Katie A HowellM Javad Aman
Oct 25, 2017·Nature Reviews. Immunology·Lenette L LuGalit Alter

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Citations

Feb 8, 2019·Journal of Virology·Lauren E WilliamsonJames E Crowe
Sep 6, 2019·Proceedings of the National Academy of Sciences of the United States of America·Stylianos BournazosJeffrey V Ravetch
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Nina G BozhanovaJens Meiler
Feb 23, 2020·Immunity·Matthias Zehner, Florian Klein
Feb 16, 2020·Cell Host & Microbe·Hadas Cohen-DvashiRon Diskin
May 6, 2021·ILAR Journal·Zachary SchiffmanLogan Banadyga
Jun 28, 2021·The Lancet Infectious Diseases·Philipp A Ilinykh, Alexander Bukreyev
Jun 15, 2021·Frontiers in Public Health·David A SpencerAnn J Hessell
Jul 16, 2021·Science Translational Medicine·Michelle MeyerAlexander Bukreyev
Sep 11, 2021·Lab on a Chip·Julie Van LentJeroen Lammertyn
Nov 2, 2021·Frontiers in Immunology·Ariel S WirchnianskiKartik Chandran
Dec 29, 2021·Expert Opinion on Drug Discovery·Steven B Bradfute

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Datasets Mentioned

BETA
AF49101
KT878488
KU174137
KU174142
KM233070
DQ447653
EMD-7955

Methods Mentioned

BETA
ELISA
flow cytometry
electron microscopy
density gradient centrifugation
enzyme-linked immunosorbent assays
fluorescence-activated cell sorting
PCR
transfection
size exclusion chromatography
column chromatography

Software Mentioned

FlowJo Star
Intellicyt
FlowJo
Relion
GraphPad
Chimera
MATLAB
Prism
Pymol Schrödinger
VetScan

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