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


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.

SUBMITTER: Gilchuk P 

PROVIDER: S-EPMC6104738 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Gilchuk Pavlo P   Kuzmina Natalia N   Ilinykh Philipp A PA   Huang Kai K   Gunn Bronwyn M BM   Bryan Aubrey A   Davidson Edgar E   Doranz Benjamin J BJ   Turner Hannah L HL   Fusco Marnie L ML   Bramble Matthew S MS   Hoff Nicole A NA   Binshtein Elad E   Kose Nurgun N   Flyak Andrew I AI   Flinko Robin R   Orlandi Chiara C   Carnahan Robert R   Parrish Erica H EH   Sevy Alexander M AM   Bombardi Robin G RG   Singh Prashant K PK   Mukadi Patrick P   Muyembe-Tamfum Jean Jacques JJ   Ohi Melanie D MD   Saphire Erica Ollmann EO   Lewis George K GK   Alter Galit G   Ward Andrew B AB   Rimoin Anne W AW   Bukreyev Alexander A   Crowe James E JE  

Immunity 20180717 2


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 bou  ...[more]

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