Details

Autor(en) / Beteiligte

• Gilchuk, Pavlo
• Kuzmina, Natalia
• Ilinykh, Philipp A.
• Huang, Kai
• Gunn, Bronwyn M.
• Bryan, Aubrey
• Davidson, Edgar
• Doranz, Benjamin J.
• Turner, Hannah L.
• Fusco, Marnie L.
• Bramble, Matthew S.
• Hoff, Nicole A.
• Binshtein, Elad
• Kose, Nurgun
• Flyak, Andrew I.
• Flinko, Robin
• Orlandi, Chiara
• Carnahan, Robert
• Parrish, Erica H.
• Sevy, Alexander M.
• Bombardi, Robin G.
• Singh, Prashant K.
• Mukadi, Patrick
• Muyembe-Tamfum, Jean Jacques
• Ohi, Melanie D.
• Saphire, Erica Ollmann
• Lewis, George K.
• Alter, Galit
• Ward, Andrew B.
• Rimoin, Anne W.
• Bukreyev, Alexander
• Crowe, James E.

Titel

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

Ist Teil von

• Immunity (Cambridge, Mass.), 2018-08, Vol.49 (2), p.363-374.e10

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •Broad human antibody recognizes a quaternary site of vulnerability on ebolavirus GP•The antibody possesses pan-ebolavirus neutralizing and protective capacity•The antibody mediates protection principally by direct virus neutralization•The antibody uses several mechanisms for contributing to broad immunity 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.