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

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

doi:10.1016/j.immuni.2018.06.018

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

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. SevyRobin 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

Pathology

Research output: Contribution to journal › Article › peer-review

58 Scopus citations

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. 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.

Original language	English (US)
Pages (from-to)	363-374.e10
Journal	Immunity
Volume	49
Issue number	2
DOIs	https://doi.org/10.1016/j.immuni.2018.06.018
State	Published - Aug 21 2018

Keywords

Ebola hemorrhagic fever
cross protection
ebolavirus
epitope mapping
epitopes
glycoproteins
heterologous immunity
monoclonal antibodies
neutralizing antibodies
viral antibodies

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

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10.1016/j.immuni.2018.06.018

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Gilchuk, P., Kuzmina, N., Ilinykh, P. A., Huang, K., Gunn, B. M., Bryan, A., Davidson, E., Doranz, B. J., Turner, H. L., Fusco, M. L., Bramble, M. S., Hoff, N. A., Binshtein, E., Kose, N., Flyak, A. I., Flinko, R., Orlandi, C., Carnahan, R., Parrish, E. H., ... Crowe, J. E. (2018). Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein. Immunity, 49(2), 363-374.e10. https://doi.org/10.1016/j.immuni.2018.06.018

Gilchuk, P, Kuzmina, N, Ilinykh, PA, Huang, K, Gunn, BM, Bryan, A, Davidson, E, Doranz, BJ, Turner, HL, Fusco, ML, Bramble, MS, Hoff, NA, Binshtein, E, Kose, N, Flyak, AI, Flinko, R, Orlandi, C, Carnahan, R, Parrish, EH, Sevy, AM, Bombardi, RG, Singh, PK, Mukadi, P, Muyembe-Tamfum, JJ, Ohi, MD, Saphire, EO, Lewis, GK, Alter, G, Ward, AB, Rimoin, AW, Bukreyev, A & Crowe, JE 2018, 'Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein', Immunity, vol. 49, no. 2, pp. 363-374.e10. https://doi.org/10.1016/j.immuni.2018.06.018

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title = "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. 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.",

keywords = "Ebola hemorrhagic fever, cross protection, ebolavirus, epitope mapping, epitopes, glycoproteins, heterologous immunity, monoclonal antibodies, neutralizing antibodies, viral antibodies",

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

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doi = "10.1016/j.immuni.2018.06.018",

language = "English (US)",

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AU - Gilchuk, Pavlo

AU - Kuzmina, Natalia

AU - Ilinykh, Philipp A.

AU - Huang, Kai

AU - Gunn, Bronwyn M.

AU - Bryan, Aubrey

AU - Davidson, Edgar

AU - Doranz, Benjamin J.

AU - Turner, Hannah L.

AU - Fusco, Marnie L.

AU - Bramble, Matthew S.

AU - Hoff, Nicole A.

AU - Binshtein, Elad

AU - Kose, Nurgun

AU - Flyak, Andrew I.

AU - Flinko, Robin

AU - Orlandi, Chiara

AU - Carnahan, Robert

AU - Parrish, Erica H.

AU - Sevy, Alexander M.

AU - Bombardi, Robin G.

AU - Singh, Prashant K.

AU - Mukadi, Patrick

AU - Muyembe-Tamfum, Jean Jacques

AU - Ohi, Melanie D.

AU - Saphire, Erica Ollmann

AU - Lewis, George K.

AU - Alter, Galit

AU - Ward, Andrew B.

AU - Rimoin, Anne W.

AU - Bukreyev, Alexander

AU - Crowe, James E.

PY - 2018/8/21

Y1 - 2018/8/21

N2 - 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. 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.

AB - 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. 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.

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KW - cross protection

KW - ebolavirus

KW - epitope mapping

KW - epitopes

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KW - heterologous immunity

KW - monoclonal antibodies

KW - neutralizing antibodies

KW - viral antibodies

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

Abstract

Keywords

ASJC Scopus subject areas

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