@article{e6e120dae951465ebf933cbb2e37d63e,
title = "Broadly neutralizing antibodies from human survivors target a conserved site in the ebola virus glycoprotein hr2-mper region",
abstract = "Ebola virus (EBOV) in humans causes a severe illness with high mortality rates. Several strategies have been developed in the past to treat EBOV infection, including the antibody cocktail ZMapp, which has been shown to be effective in nonhuman primate models of infection 1 and has been used under compassionate-Treatment protocols in humans 2 . ZMapp is a mixture of three chimerized murine monoclonal antibodies (mAbs) 3-6 that target EBOV-specific epitopes on the surface glycoprotein 7,8 . However, ZMapp mAbs do not neutralize other species from the genus Ebolavirus, such as Bundibugyo virus (BDBV), Reston virus (RESTV) or Sudan virus (SUDV). Here, we describe three naturally occurring human cross-neutralizing mAbs, from BDBV survivors, that target an antigenic site in the canonical heptad repeat 2 (HR2) region near the membrane-proximal external region (MPER) of the glycoprotein. The identification of a conserved neutralizing antigenic site in the glycoprotein suggests that these mAbs could be used to design universal antibody therapeutics against diverse ebolavirus species. Furthermore, we found that immunization with a peptide comprising the HR2-MPER antigenic site elicits neutralizing antibodies in rabbits. Structural features determined by conserved residues in the antigenic site described here could inform an epitope-based vaccine design against infection caused by diverse ebolavirus species.",
author = "Flyak, {Andrew I.} and Natalia Kuzmina and Murin, {Charles D.} and Christopher Bryan and Edgar Davidson and Pavlo Gilchuk and Gulka, {Christopher P.} and Ilinykh, {Philipp A.} and Xiaoli Shen and Kai Huang and Palaniappan Ramanathan and Hannah Turner and Fusco, {Marnie L.} and Rebecca Lampley and Nurgun Kose and Hannah King and Gopal Sapparapu and Doranz, {Benjamin J.} and Ksiazek, {Thomas G.} and Wright, {David W.} and Saphire, {Erica Ollmann} and Ward, {Andrew B.} and Alexander Bukreyev and Crowe, {James E.}",
note = "Funding Information: This project received support from the Defense Threat Reduction Agency (grant HDTRA1-13-1-0034 to J.E.C. and A.B.), US NIH grants U19 AI109711 (to J.E.C. and A.B.), U19 AI109762 (to E.O.S. and A.B.W.), NIH contract HHSN272201400058C (to B.J.D.) and R01 AI067927 (to E.O.S.). E.O.S. is an investigator in the Pathogenesis of Infectious Disease of the Burroughs Wellcome Fund. The project was supported by NCRR grant UL1 RR024975-01 and is now at the National Center for Advancing Translational Sciences, grant 2 UL1 TR000445-06. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We thank S. Graham and L. Loerinc at Vanderbilt University for help with the expression of recombinant antibodies. We thank P. Younan at UTMB for assisting with statistical calculations. We also thank A. McNeal, S. Reddy and R. Fong for technical help with shotgun mutagenesis epitope mapping. C.D.M. is supported by a National Science Foundation Graduate Research Fellowship. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = jun,
day = "1",
doi = "10.1038/s41564-018-0157-z",
language = "English (US)",
volume = "3",
pages = "670--677",
journal = "Nature Microbiology",
issn = "2058-5276",
publisher = "Nature Publishing Group",
number = "6",
}