Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein
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AbstractEbolaviruses 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. Ebola virus, a member of the Filoviridae family, causes severe disease in humans. Gilchuk et al. isolated and characterized broadly neutralizing human monoclonal antibodies active against all three clinically relevant ebolavirus species. Potent monoclonal antibody EBOV-520 binds to the glycoprotein base region, acts principally by direct virus neutralization, and exploits several mechanisms for contributing to pan-ebolavirus protective immunity. Copyright 2018 The Author(s)
SponsorsThis work was supported by U.S. NIH grants U19 AI109711 (to J.E.C. and A. Bukreyev), R01 AI067927 (to E.O.S.), and U19 AI109762 (to E.O.S. and A.B.W.), Defense Threat Reduction Agency grant HDTRA1-13-1-0034 (to J.E.C. and A. Bukreyev), HHS contract HHSN272201400058C (to J.E.C. and B.J.D.), Defense Advanced Research Project Agency grant W31P4Q-14-1-0010 (to J.E.C.), Fogarty International Center of the National Institutes of Health (NIH) under award number D43TW009343 and the University of California Global Health Institute (UCGHI) (to M.S.B.), and funding from the Bill and Melinda Gates Foundation (to J.E.C. and A.W.R. by subcontract from Atreca, Inc.). E.O.S. is an Investigator in the Pathogenesis of Infectious Disease of the Burroughs Welcome Fund . The project was supported by NCRR grant UL1 RR024975-01 , which is now at the National Center for Advancing Translational Sciences , grant 2 UL1 TR000445-06 .
Ebola hemorrhagic fever
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85053075312&doi=10.1016%2fj.immuni.2018.06.018&partnerID=40&md5=3c7074125be477f7489308955a669525; http://hdl.handle.net/10713/9770
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