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Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp

Author

Listed:
  • 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
    University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada)

  • Jonathan Audet

    (National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
    University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada)

  • Alexander Bello

    (National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
    University of Manitoba, Winnipeg, Manitoba R3E 0J9, 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
    University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada)

  • Haiyan Wei

    (National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
    Institute of Infectious Disease, Henan Centre for Disease Control and Prevention, Zhengzhou, 450012 Henan, China)

  • 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)
    Present address: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland 21702, USA.)

  • Gene G. Olinger

    (United States Army Medical Research Institute of Infectious Diseases (USAMRIID)
    Present address: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland 21702, USA.)

  • 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
    University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada
    University of Manitoba, Winnipeg, Manitoba R3A 1S1, 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
    University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada
    University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada
    University of Pennsylvania School of Medicine)

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.

Suggested Citation

  • 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 & Kel, 2014. "Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp," Nature, Nature, vol. 514(7520), pages 47-53, October.
    • Handle: RePEc:nat:nature:v:514:y:2014:i:7520:d:10.1038_nature13777
    DOI: 10.1038/nature13777
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    Cited by:

    1. Surender Khurana & Gabrielle Grubbs & Supriya Ravichandran & Emily Cluff & JungHyun Kim & Ana I. Kuehne & Samantha Zak & John M. Dye & Julius J. Lutwama & Andrew S. Herbert, 2024. "Longitudinal proteome-wide antibody profiling in Marburg virus survivors identifies wing domain immunogen for vaccine design," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Zhang, Kebo & Hong, Xiao & Han, Yuexing & Wang, Bing, 2023. "Optimal discrete resource allocation on metapopulation networks for suppressing spatial spread of epidemic," Chaos, Solitons & Fractals, Elsevier, vol. 169(C).
    3. Franziska K. Kaiser & Mariana Gonzalez Hernandez & Nadine Krüger & Ellinor Englund & Wenjuan Du & Anna Z. Mykytyn & Mathijs P. Raadsen & Mart M. Lamers & Francine Rodrigues Ianiski & Tatiana M. Shamor, 2024. "Filamentous fungus-produced human monoclonal antibody provides protection against SARS-CoV-2 in hamster and non-human primate models," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Wataru Nishi & Ei Wakamatsu & Hiroaki Machiyama & Ryohei Matsushima & Kensho Saito & Yosuke Yoshida & Tetsushi Nishikawa & Tomohiro Takehara & Hiroko Toyota & Masae Furuhata & Hitoshi Nishijima & Arat, 2023. "Evaluation of therapeutic PD-1 antibodies by an advanced single-molecule imaging system detecting human PD-1 microclusters," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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