@article{c7f8f623e69d4dd0b2e91ad23e204659,
title = "Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization",
abstract = "Cooperative interactions of monoclonal antibodies (mAbs) with viral antigens are poorly understood. Gilchuk et al. perform structural and functional analysis of cooperativity in a cocktail of two human mAbs, recognizing major epitopes of ebolavirus glycoprotein (GP), and define cooperative binding of the GP as a mechanism for enhanced ebolavirus neutralization.",
keywords = "Ebolavirus, antibody synergy, antibody therapeutics, cooperative neutralization, ebolavirus infection, epitope mapping, glycoprotein, molecular mimicry, neutralizing antibodies, viral antibodies",
author = "Pavlo Gilchuk and Murin, {Charles D.} and Milligan, {Jacob C.} and Cross, {Robert W.} and Chad Mire and Ilinykh, {Philipp A.} and Kai Huang and Natalia Kuzmina and Altman, {Pilar X.} and Sean Hui and Gunn, {Bronwyn M.} and Bryan, {Aubrey L.} and Edgar Davidson and Doranz, {Benjamin J.} and Turner, {Hannah L.} and Tanwee Alkutkar and Robin Flinko and Chiara Orlandi and Robert Carnahan and Rachel Nargi and Bombardi, {Robin G.} and Vodzak, {Megan E.} and Sheng Li and Adaora Okoli and Morris Ibeawuchi and Benjamin Ohiaeri and Lewis, {George K.} and Galit Alter and Alexander Bukreyev and Saphire, {Erica Ollmann} and Geisbert, {Thomas W.} and Ward, {Andrew B.} and Crowe, {James E.}",
note = "Funding Information: We thank J. Slaughter, C. Schoeder, N. Kose, S. Smith, K. Schey, W. White, J.D. Laughlin, J. Geisbert, K. Agans, D. Deer, and V. Borisevich for technical assistance. The Jurkat-EBOV, Jurkat-BDBV, and Jurkat-SUDV GP cell lines were a kind gift from C. Davis and R. Ahmed. This work was supported by US NIH grants U19 AI109711 to J.E.C. and A.B. U19 AI142785 to J.E.C. and T.G. R01 AI067927 to E.O.S. and U19 AI109762 to E.O.S. and A.B.W.); the U.S. Department of Health and Human Services (HHS) contract HHSN272201400058C to J.E.C. and B.J.D.; Defense Threat Reduction Agency (DTRA) grant HDTRA1-13-1-0034 to J.E.C. and A.B.; Defense Advanced Reseach Projects Agency (DARPA) grant W31P4Q-14-1-0010 to J.E.C.; Fogarty International Center of the NIH under award number D43TW009343; and the University of California Global Health Institute (UCGHI) to M.S.B.; and funding from the Bill and Melinda Gates Foundation to. J.E.C. by subcontract from Atreca, Inc. E.O.S. is an Investigator in the Pathogenesis of Infectious Disease of the Burroughs Welcome Fund. The project was supported by NCRR grant UL1 RR024975-01, which 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. Work in BSL-4 and ABSL-4 was supported by NIH grant 5UC7AI094660-07 and by the Animal Resource Center of the Galveston National Laboratory. P.G. C.D.M. B.J.D. R.C. G.K.L. G.A. A. Bukreyev, A.B.W. E.O.S. T.W.G. and J.E.C. planned the studies. P.G. C.D.M. P.A.I. K.H. N.K. R.W.C. C.E.M. J.C.M. P.X.A. S.H. B.M.G. A.L.B. E.D. H.L.T. T.A. R.F. C.O. R.N. R.G.B. S.L. M.E.V. and T.W.G. conducted experiments. A.O. M.I. and B.O. assisted with human sample acquisition. P.G. C.D.M. J.C.M. B.M.G. G.K.L. E.O.S. A.B.W. A. Bukreyev, and J.E.C. interpreted the studies. P.G. and J.E.C. wrote the first draft of the paper. E.O.S. B.J.D, A.B, T.W.G. and J.E.C. obtained funding. All authors reviewed, edited, and approved the paper. A.L.B. E.D. and B.J.D. are employees of Integral Molecular. B.J.D. is a shareholder of Integral Molecular. J.E.C. has served as a consultant for Sanofi and is on the Scientific Advisory Boards of CompuVax and Meissa Vaccines, is a recipient of previous unrelated research grants from Moderna and Sanofi, and is founder of IDBiologics. Vanderbilt University has applied for a patent that is related to this work. All other authors declare no competing interests. Funding Information: We thank J. Slaughter, C. Schoeder, N. Kose, S. Smith, K. Schey, W. White, J.D. Laughlin, J. Geisbert, K. Agans, D. Deer, and V. Borisevich for technical assistance. The Jurkat-EBOV, Jurkat-BDBV, and Jurkat-SUDV GP cell lines were a kind gift from C. Davis and R. Ahmed. This work was supported by US NIH grants U19 AI109711 to J.E.C. and A.B., U19 AI142785 to J.E.C. and T.G., R01 AI067927 to E.O.S., and U19 AI109762 to E.O.S. and A.B.W.); the U.S. Department of Health and Human Services ( HHS) contract HHSN272201400058C to J.E.C. and B.J.D.; Defense Threat Reduction Agency ( DTRA) grant HDTRA1-13-1-0034 to J.E.C. and A.B.; Defense Advanced Reseach Projects Agency ( DARPA) grant W31P4Q-14-1-0010 to J.E.C.; Fogarty International Center of the NIH under award number D43TW009343 ; and the University of California Global Health Institute (UCGHI) to M.S.B.; and funding from the Bill and Melinda Gates Foundation to. J.E.C. by subcontract from Atreca, Inc. E.O.S. is an Investigator in the Pathogenesis of Infectious Disease of the Burroughs Welcome Fund . The project was supported by NCRR grant UL1 RR024975-01 , which 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. Work in BSL-4 and ABSL-4 was supported by NIH grant 5UC7AI094660-07 and by the Animal Resource Center of the Galveston National Laboratory . Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = feb,
day = "18",
doi = "10.1016/j.immuni.2020.01.001",
language = "English (US)",
volume = "52",
pages = "388--403.e12",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "2",
}