Antibody Treatment of Ebola and Sudan Virus Infection via a Uniquely Exposed Epitope within the Glycoprotein Receptor-Binding Site

Katie A. Howell, Xiangguo Qiu, Jennifer M. Brannan, Christopher Bryan, Edgar Davidson, Frederick W. Holtsberg, Anna Z. Wec, Sergey Shulenin, Julia E. Biggins, Robin Douglas, Sven G. Enterlein, Hannah L. Turner, Jesper Pallesen, Charles D. Murin, Shihua He, Andrea Kroeker, Hong Vu, Andrew S. Herbert, Marnie L. Fusco, Elisabeth K. NyakaturaJonathan R. Lai, Zhen Yong Keck, Steven K H Foung, Erica Ollmann Saphire, Larry Zeitlin, Andrew B. Ward, Kartik Chandran, Benjamin J. Doranz, Gary P. Kobinger, John M. Dye, M. Javad Aman

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45 Scopus citations

Abstract

Previous efforts to identify cross-neutralizing antibodies to the receptor-binding site (RBS) of ebolavirus glycoproteins have been unsuccessful, largely because the RBS is occluded on the viral surface. We report a monoclonal antibody (FVM04) that targets a uniquely exposed epitope within the RBS; cross-neutralizes Ebola (EBOV), Sudan (SUDV), and, to a lesser extent, Bundibugyo viruses; and shows protection against EBOV and SUDV in mice and guinea pigs. The antibody cocktail ZMapp™ is remarkably effective against EBOV (Zaire) but does not cross-neutralize other ebolaviruses. By replacing one of the ZMapp™ components with FVM04, we retained the anti-EBOV efficacy while extending the breadth of protection to SUDV, thereby generating a cross-protective antibody cocktail. In addition, we report several mutations at the base of the ebolavirus glycoprotein that enhance the binding of FVM04 and other cross-reactive antibodies. These findings have important implications for pan-ebolavirus vaccine development and defining broadly protective antibody cocktails.

Original languageEnglish (US)
Pages (from-to)1514-1526
Number of pages13
JournalCell Reports
Volume15
Issue number7
DOIs
StatePublished - May 17 2016

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Howell, K. A., Qiu, X., Brannan, J. M., Bryan, C., Davidson, E., Holtsberg, F. W., Wec, A. Z., Shulenin, S., Biggins, J. E., Douglas, R., Enterlein, S. G., Turner, H. L., Pallesen, J., Murin, C. D., He, S., Kroeker, A., Vu, H., Herbert, A. S., Fusco, M. L., ... Aman, M. J. (2016). Antibody Treatment of Ebola and Sudan Virus Infection via a Uniquely Exposed Epitope within the Glycoprotein Receptor-Binding Site. Cell Reports, 15(7), 1514-1526. https://doi.org/10.1016/j.celrep.2016.04.026