@article{c96ee1eade2f41f7885fc9c30b7a47e9,
title = "Antibody Treatment of Ebola and Sudan Virus Infection via a Uniquely Exposed Epitope within the Glycoprotein Receptor-Binding Site",
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{\texttrademark} is remarkably effective against EBOV (Zaire) but does not cross-neutralize other ebolaviruses. By replacing one of the ZMapp{\texttrademark} 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.",
author = "Howell, {Katie A.} and Xiangguo Qiu and Brannan, {Jennifer M.} and Christopher Bryan and Edgar Davidson and Holtsberg, {Frederick W.} and Wec, {Anna Z.} and Sergey Shulenin and Biggins, {Julia E.} and Robin Douglas and Enterlein, {Sven G.} and Turner, {Hannah L.} and Jesper Pallesen and Murin, {Charles D.} and Shihua He and Andrea Kroeker and Hong Vu and Herbert, {Andrew S.} and Fusco, {Marnie L.} and Nyakatura, {Elisabeth K.} and Lai, {Jonathan R.} and Keck, {Zhen Yong} and Foung, {Steven K.H.} and Saphire, {Erica Ollmann} and Larry Zeitlin and Ward, {Andrew B.} and Kartik Chandran and Doranz, {Benjamin J.} and Kobinger, {Gary P.} and Dye, {John M.} and Aman, {M. Javad}",
note = "Funding Information: This work was supported by a contract (HDTRA1-13-C-0015) from the U.S. Defense Threat Reduction Agency (DTRA) to M.J.A., grant U19 AI109762 from the NIH to E.O.S., and NIH contract HHSN272201400058C to B.J.D. J.R.L. acknowledges funding from the NIH (U19AI109762). This work was also partially supported by the Public Health Agency of Canada (PHAC). We thank Andrew McNeal and Rachel Fong for valuable technical assistance. C.D.M. is supported by a pre-doctoral fellowship from the National Science Foundation. E.K.N. was supported by a DAAD (Deutscher Akademischer Austauschdienst [German Academic Exchange Service]) fellowship. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. M.J.A. is a shareholder of Integrated Biotherapeutics. S.G.E., F.W.H., H.V., R.D., and S.S. own stock options in Integrated Biotherapeutics. Publisher Copyright: {\textcopyright} 2016 The Authors.",
year = "2016",
month = may,
day = "17",
doi = "10.1016/j.celrep.2016.04.026",
language = "English (US)",
volume = "15",
pages = "1514--1526",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "7",
}