@article{bb34afe1609540a89bcabb2881d5c219,
title = "Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses",
abstract = "Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes. Only a few somatic hypermutations are required for broad antiviral activity, and germline-approximating variants display enhanced GPCL recognition, suggesting that such antibodies could be elicited more efficiently with suitably optimized GP immunogens. Our findings inform the development of both broadly effective immunotherapeutics and vaccines against filoviruses.",
keywords = "15878, EBOV, Ebola virus, ebolavirus, ferret, human broadly neutralizing antibodies, infection, mouse, neutralization, protection",
author = "Wec, {Anna Z.} and Herbert, {Andrew S.} and Murin, {Charles D.} and Nyakatura, {Elisabeth K.} and Abelson, {Dafna M.} and Fels, {J. Maximilian} and Shihua He and James, {Rebekah M.} and {de La Vega}, {Marc Antoine} and Wenjun Zhu and Bakken, {Russell R.} and Eileen Goodwin and Turner, {Hannah L.} and Jangra, {Rohit K.} and Larry Zeitlin and Xiangguo Qiu and Lai, {Jonathan R.} and Walker, {Laura M.} and Ward, {Andrew B.} and Dye, {John M.} and Kartik Chandran and Bornholdt, {Zachary A.}",
note = "Funding Information: We thank C. Harold, T. Alkutkar, and T.B. Krause for technical assistance. Support for this work was provided by NIH grants U19 AI109762 (Centers for Excellence in Translational Research) to K.C., J.R.L., J.M.D., A.B.W., X.Q., and L.Z., DTRA contract HDTRA1-13-C-0018 to L.Z., D.M.A., and Z.A.B., and DTRA contract CB4088 to A.S.H., R.R.B., R.M.J., and J.M.D. X.Q. was also supported by Public Health Agency of Canada. E.K.N. was also supported by a DAAD (Deutscher Akademischer Austauschdienst, German Academic Exchange Service) fellowship. Opinions, conclusions, interpretations, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Department of the Army and the U.S. Department of Defense. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = may,
day = "18",
doi = "10.1016/j.cell.2017.04.037",
language = "English (US)",
volume = "169",
pages = "878--890.e15",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}
