@article{354258d40f5548f29e0b6c689254214e,
title = "Emergence of Ebola Virus Escape Variants in Infected Nonhuman Primates Treated with the MB-003 Antibody Cocktail",
abstract = "MB-003, a plant-derived monoclonal antibody cocktail used effectively in treatment of Ebola virus infection in non-human primates, was unable to protect two of six animals when initiated 1 or 2 days post-infection. We characterized a mechanism of viral escape in one of the animals, after observation of two clusters of genomic mutations that resulted in five nonsynonymous mutations in the monoclonal antibody target sites. These mutations were linked to a reduction in antibody binding and later confirmed to be present in a viral isolate that was not neutralized in vitro. Retrospective evaluation of a second independent study allowed the identification of a similar case. Four SNPs in previously identified positions were found in this second fatality, suggesting that genetic drift could be a potential cause for treatment failure. These findings highlight the importance selecting different target domains for each component of the cocktail to minimize the potential for viral escape.",
author = "Kugelman, {Jeffrey R.} and Johanny Kugelman-Tonos and Ladner, {Jason T.} and James Pettit and Keeton, {Carolyn M.} and Nagle, {Elyse R.} and Garcia, {Karla Y.} and Froude, {Jeffrey W.} and Kuehne, {Ana I.} and Kuhn, {Jens H.} and Sina Bavari and Larry Zeitlin and Dye, {John M.} and Olinger, {Gene G.} and Mariano Sanchez-Lockhart and Palacios, {Gustavo F.}",
note = "Funding Information: The authors thank Dr. W. Ian Lipkin for critical review of this manuscript, Dr. Krishna Kota for advice on the high content imaging systems used in the work, and the USAMRIID technicians: Guido Pelaez and Sarah Becker in the USAMRIID Molecular and Translational Sciences Division. This work was supported by Defense Threat Reduction Agency. The content of this publication does not necessarily reflect the views or policies of the US Department of the Army, the US Department of Defense, or the US Department of Health and Human Services or of the institutions and companies affiliated with the authors. J.H.K. performed this work as an employee of Tunnell Government Services, Inc., and G.G.O. and J.P. as employees of MRI Global, both subcontractors to Battelle Memorial Institute under its prime contract with NIAID, under contract HHSN272200700016I. Publisher Copyright: {\textcopyright} 2015 The Authors.",
year = "2015",
month = sep,
day = "29",
doi = "10.1016/j.celrep.2015.08.038",
language = "English (US)",
volume = "12",
pages = "2111--2120",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "12",
}