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 KsiazekErica Ollmann Saphire, Andrew B. Ward, Alexander Bukreyev, James E. Crowe

Research output: Contribution to journalArticle

87 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)392-405
Number of pages14
JournalCell
Volume164
Issue number3
DOIs
StatePublished - Jan 28 2016

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Ebolavirus
Neutralizing Antibodies
Viruses
Antibody Formation
Infection
Monoclonal Antibodies
Polysaccharides
Antibodies
Cross Protection
Sudan
Uganda
Disease Outbreaks
Epitopes
Blood Cells
Glycoproteins
Guinea Pigs
B-Lymphocytes
Blood
Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Flyak, A. I., Shen, X., Murin, C. D., Turner, H. L., David, J. A., Fusco, M. L., ... 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

Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection. / Flyak, Andrew I.; Shen, Xiaoli; Murin, Charles D.; Turner, Hannah L.; David, Joshua A.; Fusco, Marnie L.; Lampley, Rebecca; Kose, Nurgun; Ilinykh, Philipp A.; Kuzmina, Natalia; Branchizio, Andre; King, Hannah; Brown, Leland; Bryan, Christopher; Davidson, Edgar; Doranz, Benjamin J.; Slaughter, James C.; Sapparapu, Gopal; Klages, Curtis; Ksiazek, Thomas; Saphire, Erica Ollmann; Ward, Andrew B.; Bukreyev, Alexander; Crowe, James E.

In: Cell, Vol. 164, No. 3, 28.01.2016, p. 392-405.

Research output: Contribution to journalArticle

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, T, 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
Flyak, Andrew I. ; Shen, Xiaoli ; Murin, Charles D. ; Turner, Hannah L. ; David, Joshua A. ; Fusco, Marnie L. ; Lampley, Rebecca ; Kose, Nurgun ; Ilinykh, Philipp A. ; Kuzmina, Natalia ; Branchizio, Andre ; King, Hannah ; Brown, Leland ; Bryan, Christopher ; Davidson, Edgar ; Doranz, Benjamin J. ; Slaughter, James C. ; Sapparapu, Gopal ; Klages, Curtis ; Ksiazek, Thomas ; Saphire, Erica Ollmann ; Ward, Andrew B. ; Bukreyev, Alexander ; Crowe, James E. / Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection. In: Cell. 2016 ; Vol. 164, No. 3. pp. 392-405.
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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.

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