@article{a07e5409b4274af4961c344d3f2ced63,
title = "Development of an antibody cocktail for treatment of Sudan virus infection",
abstract = "Antibody-based therapies are a promising treatment option for managing ebolavirus infections. Several Ebola virus (EBOV)-specific and, more recently, pan-ebolavirus antibody cocktails have been described. Here, we report the development and assessment of a Sudan virus (SUDV)-specific antibody cocktail. We produced a panel of SUDV glycoprotein (GP)-specific human chimeric monoclonal antibodies (mAbs) using both plant and mammalian expression systems and completed head-to-head in vitro and in vivo evaluations. Neutralizing activity, competitive binding groups, and epitope specificity of SUDV mAbs were defined before assessing protective efficacy of individual mAbs using a mouse model of SUDV infection. Of the mAbs tested, GP base-binding mAbs were more potent neutralizers and more protective than glycan cap- or mucin-like domain-binding mAbs. No significant difference was observed between plant and mammalian mAbs in any of our in vitro or in vivo evaluations. Based on in vitro and rodent testing, a combination of two SUDV-specific mAbs, one base binding (16F6) and one glycan cap binding (X10H2), was down-selected for assessment in a macaque model of SUDV infection. This cocktail, RIID F6-H2, provided protection from SUDV infection in rhesus macaques when administered at 50 mg/kg on days 4 and 6 postinfection. RIID F6-H2 is an effective postexposure SUDV therapy and provides a potential treatment option for managing human SUDV infection.",
keywords = "Ebolavirus, Monoclonal antibody, Sudan virus, Therapy | cocktail",
author = "Herbert, {Andrew S.} and Froude, {Jeffery W.} and Ortiz, {Ramon A.} and Kuehne, {Ana I.} and Dorosky, {Danielle E.} and Bakken, {Russell R.} and Zak, {Samantha E.} and Josleyn, {Nicole M.} and Konstantin Musiychuk and {Mark Jones}, R. and Brian Green and Streatfield, {Stephen J.} and Wec, {Anna Z.} and Natasha Bohorova and Ognian Bohorov and Kim, {Do H.} and Pauly, {Michael H.} and Jesus Velasco and Whaley, {Kevin J.} and Stonier, {Spencer W.} and Bornholdt, {Zachary A.} and Kartik Chandran and Larry Zeitlin and Darryl Sampey and Vidadi Yusibov and Dye, {John M.}",
note = "Funding Information: ACKNOWLEDGMENTS. We thank USAMRIID{\textquoteright}s Veterinary Medicine Division for technical assistance with animal studies and USAMRIID{\textquoteright}s Diagnostics Systems Division for technical assistance with RT-PCR analysis. We thank The Geneva Foundation, specifically Audra Earl and Andrea Masterson, for grants management and administrative support. We thank Hong Bi, Shireen Shaikh, Andrew Jenner, Stephen Tottey, and Annamalai Padmanaban (Fraunhofer USA) for technical assistance and Caitlin Morris (Fraunhofer USA) for manuscript review. Funding: This work was supported by the National Institutes of Health grant R01AI111516 and the Defense Threat Reduction Agency grant CB4088 (to J.M.D.), and the National Institutes of Health grant R01AI132256 (to K.C.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Opinions, conclusions, interpretations, and recommendations are those of the authors and are not necessarily endorsed by the US Army. The mention of trade names or commercial products does not constitute endorsement or recommendation for use by the Department of the Army or the Department of Defense.",
year = "2020",
month = feb,
day = "18",
doi = "10.1073/pnas.1914985117",
language = "English (US)",
volume = "117",
pages = "3768--3778",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "7",
}