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

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 ebo...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104738/
https://www.ncbi.nlm.nih.gov/pubmed/30029854
http://dx.doi.org/10.1016/j.immuni.2018.06.018
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author 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.
author_facet 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.
author_sort Gilchuk, Pavlo
collection PubMed
description 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.
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spelling pubmed-61047382018-08-23 Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein 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. Immunity Article 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. Cell Press 2018-08-21 /pmc/articles/PMC6104738/ /pubmed/30029854 http://dx.doi.org/10.1016/j.immuni.2018.06.018 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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.
Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein
title Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein
title_full Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein
title_fullStr Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein
title_full_unstemmed Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein
title_short Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein
title_sort multifunctional pan-ebolavirus antibody recognizes a site of broad vulnerability on the ebolavirus glycoprotein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104738/
https://www.ncbi.nlm.nih.gov/pubmed/30029854
http://dx.doi.org/10.1016/j.immuni.2018.06.018
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