Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp

Xiangguo Qiu, Gary Wong, Jonathan Audet, Alexander Bello, Lisa Fernando, Judie B. Alimonti, Hugues Fausther-Bovendo, Haiyan Wei, Jenna Aviles, Ernie Hiatt, Ashley Johnson, Josh Morton, Kelsi Swope, Ognian Bohorov, Natasha Bohorova, Charles Goodman, Do Kim, Michael H. Pauly, Jesus Velasco, James Pettitt, Gene G. Olinger, Kevin Whaley, Bianli Xu, James E. Strong, Larry Zeitlin () and Gary P. Kobinger ()
Additional contact information
Xiangguo Qiu: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
Gary Wong: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
Jonathan Audet: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
Alexander Bello: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
Lisa Fernando: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
Judie B. Alimonti: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
Hugues Fausther-Bovendo: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
Haiyan Wei: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
Jenna Aviles: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
Ernie Hiatt: Kentucky BioProcessing
Ashley Johnson: Kentucky BioProcessing
Josh Morton: Kentucky BioProcessing
Kelsi Swope: Kentucky BioProcessing
Ognian Bohorov: Mapp Biopharmaceutical Inc.
Natasha Bohorova: Mapp Biopharmaceutical Inc.
Charles Goodman: Mapp Biopharmaceutical Inc.
Do Kim: Mapp Biopharmaceutical Inc.
Michael H. Pauly: Mapp Biopharmaceutical Inc.
Jesus Velasco: Mapp Biopharmaceutical Inc.
James Pettitt: United States Army Medical Research Institute of Infectious Diseases (USAMRIID)
Gene G. Olinger: United States Army Medical Research Institute of Infectious Diseases (USAMRIID)
Kevin Whaley: Mapp Biopharmaceutical Inc.
Bianli Xu: Institute of Infectious Disease, Henan Centre for Disease Control and Prevention, Zhengzhou, 450012 Henan, China
James E. Strong: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
Larry Zeitlin: Mapp Biopharmaceutical Inc.
Gary P. Kobinger: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada

Nature, 2014, vol. 514, issue 7520, 47-53

Abstract: Abstract Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use.

Date: 2014
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DOI: 10.1038/nature13777

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