Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection

Andrew I. Flyak; Xiaoli Shen; Charles D. Murin; Hannah L. Turner; Joshua A. David; Marnie L. Fusco; Rebecca Lampley; Nurgun Kose; Philipp A. Ilinykh; Natalia Kuzmina; Andre Branchizio; Hannah King; Leland Brown; Christopher Bryan; Edgar Davidson; Benjamin J. Doranz; James C. Slaughter; Gopal Sapparapu; Curtis Klages; Thomas G. Ksiazek; Erica Ollmann Saphire; Andrew B. Ward; Alexander Bukreyev; James E. Crowe

doi:10.1016/j.cell.2015.12.022

Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection

Andrew I. Flyak, Xiaoli Shen, Charles D. Murin, Hannah L. Turner, Joshua A. David, Marnie L. Fusco, Rebecca Lampley, Nurgun Kose, Philipp A. Ilinykh, Natalia Kuzmina, Andre Branchizio, Hannah King, Leland Brown, Christopher Bryan, Edgar Davidson, Benjamin J. Doranz, James C. Slaughter, Gopal Sapparapu, Curtis Klages, Thomas G. KsiazekErica Ollmann Saphire, Andrew B. Ward, Alexander Bukreyev, James E. Crowe

Pathology

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

148 Scopus citations

Abstract

Summary Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV), and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses, including SUDV, and a cross-reactive mAb that completely protected Guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections.

Original language	English (US)
Pages (from-to)	392-405
Number of pages	14
Journal	Cell
Volume	164
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2015.12.022
State	Published - Jan 28 2016

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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Flyak, A. I., Shen, X., Murin, C. D., Turner, H. L., David, J. A., Fusco, M. L., Lampley, R., Kose, N., Ilinykh, P. A., Kuzmina, N., Branchizio, A., King, H., Brown, L., Bryan, C., Davidson, E., Doranz, B. J., Slaughter, J. C., Sapparapu, G., Klages, C., ... Crowe, J. E. (2016). Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection. Cell, 164(3), 392-405. https://doi.org/10.1016/j.cell.2015.12.022

Flyak, AI, Shen, X, Murin, CD, Turner, HL, David, JA, Fusco, ML, Lampley, R, Kose, N, Ilinykh, PA, Kuzmina, N, Branchizio, A, King, H, Brown, L, Bryan, C, Davidson, E, Doranz, BJ, Slaughter, JC, Sapparapu, G, Klages, C, Ksiazek, TG, Saphire, EO, Ward, AB, Bukreyev, A & Crowe, JE 2016, 'Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection', Cell, vol. 164, no. 3, pp. 392-405. https://doi.org/10.1016/j.cell.2015.12.022

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title = "Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection",

abstract = "Summary Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV), and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses, including SUDV, and a cross-reactive mAb that completely protected Guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections.",

author = "Flyak, {Andrew I.} and Xiaoli Shen and Murin, {Charles D.} and Turner, {Hannah L.} and David, {Joshua A.} and Fusco, {Marnie L.} and Rebecca Lampley and Nurgun Kose and Ilinykh, {Philipp A.} and Natalia Kuzmina and Andre Branchizio and Hannah King and Leland Brown and Christopher Bryan and Edgar Davidson and Doranz, {Benjamin J.} and Slaughter, {James C.} and Gopal Sapparapu and Curtis Klages and Ksiazek, {Thomas G.} and Saphire, {Erica Ollmann} and Ward, {Andrew B.} and Alexander Bukreyev and Crowe, {James E.}",

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AU - Flyak, Andrew I.

AU - Shen, Xiaoli

AU - Murin, Charles D.

AU - Turner, Hannah L.

AU - David, Joshua A.

AU - Fusco, Marnie L.

AU - Lampley, Rebecca

AU - Kose, Nurgun

AU - Ilinykh, Philipp A.

AU - Kuzmina, Natalia

AU - Branchizio, Andre

AU - King, Hannah

AU - Brown, Leland

AU - Bryan, Christopher

AU - Davidson, Edgar

AU - Doranz, Benjamin J.

AU - Slaughter, James C.

AU - Sapparapu, Gopal

AU - Klages, Curtis

AU - Ksiazek, Thomas G.

AU - Saphire, Erica Ollmann

AU - Ward, Andrew B.

AU - Bukreyev, Alexander

AU - Crowe, James E.

PY - 2016/1/28

Y1 - 2016/1/28

N2 - Summary Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV), and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses, including SUDV, and a cross-reactive mAb that completely protected Guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections.

AB - Summary Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV), and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses, including SUDV, and a cross-reactive mAb that completely protected Guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections.

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Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection

Abstract

ASJC Scopus subject areas

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