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Title | Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein. |
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Journal, issue, pages | Immunity, Vol. 49, Issue 2, Page 363-374.e10, Year 2018 |
Publish date | Aug 21, 2018 |
Authors | Pavlo Gilchuk / Natalia Kuzmina / Philipp A Ilinykh / Kai Huang / Bronwyn M Gunn / Aubrey Bryan / Edgar Davidson / Benjamin J Doranz / Hannah L Turner / Marnie L Fusco / Matthew S Bramble / Nicole A Hoff / Elad Binshtein / Nurgun Kose / Andrew I Flyak / Robin Flinko / Chiara Orlandi / Robert Carnahan / Erica H Parrish / Alexander M Sevy / Robin G Bombardi / Prashant K Singh / Patrick Mukadi / Jean Jacques Muyembe-Tamfum / Melanie D Ohi / Erica Ollmann Saphire / George K Lewis / Galit Alter / Andrew B Ward / Anne W Rimoin / Alexander Bukreyev / James E Crowe / |
PubMed 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 ...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. |
External links | Immunity / PubMed:30029854 / PubMed Central |
Methods | EM (single particle) |
Resolution | 13.4 - 18.45 Å |
Structure data | EMDB-7955: EMDB-7956: |
Source |
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