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.

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Acknowledgements

The authors thank K. Tierney, A. Grolla, S. Jones, J. Dong and D. Kobasa for their technical assistance, V. Klimyuk and Y. Gleba for access to the magnICON expression system, and H. Steinkellner for access to transgenic N. benthamiana. This work was supported by the Defense Threat Reduction Agency (DTRA contract HDTRA1-13-C-0018), the National Institutes of Health (U19AI109762), the Public Health Agency of Canada (PHAC), and a Canadian Safety and Security Program (CSSP) grant to G.P.K. and X.Q. G.W. is the recipient of a Doctoral Research Award from the Canadian Institute for Health Research (CIHR).

Author information

Author notes

    • James Pettitt
    •  & Gene G. Olinger

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

Affiliations

  1. National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada

    • Xiangguo Qiu
    • , Gary Wong
    • , Jonathan Audet
    • , Alexander Bello
    • , Lisa Fernando
    • , Judie B. Alimonti
    • , Hugues Fausther-Bovendo
    • , Haiyan Wei
    • , Jenna Aviles
    • , James E. Strong
    •  & Gary P. Kobinger
  2. Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada

    • Gary Wong
    • , Jonathan Audet
    • , Alexander Bello
    • , Hugues Fausther-Bovendo
    • , James E. Strong
    •  & Gary P. Kobinger
  3. Institute of Infectious Disease, Henan Centre for Disease Control and Prevention, Zhengzhou, 450012 Henan, China

    • Haiyan Wei
    •  & Bianli Xu
  4. Kentucky BioProcessing, Owensboro, Kentucky 42301, USA

    • Ernie Hiatt
    • , Ashley Johnson
    • , Josh Morton
    •  & Kelsi Swope
  5. Mapp Biopharmaceutical Inc., San Diego, California 92121, USA

    • Ognian Bohorov
    • , Natasha Bohorova
    • , Charles Goodman
    • , Do Kim
    • , Michael H. Pauly
    • , Jesus Velasco
    • , Kevin Whaley
    •  & Larry Zeitlin
  6. United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland 21702, USA

    • James Pettitt
    •  & Gene G. Olinger
  7. Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba R3A 1S1, Canada

    • James E. Strong
  8. Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada

    • Gary P. Kobinger
  9. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA

    • Gary P. Kobinger

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Contributions

X.Q., G.P.K. and L.Z. designed the experiments. X.Q., G.W., J.A., A.B., L.F., J.B.A., H.F., H.W., J.A., J. P., G.G.O. and G.P.K. performed the experiments. X.Q., G.W., J.A., K.W., B.X., J.E.S., L.Z. and G.P.K. wrote the manuscript. E.H., A.J., J.M., K.S., O.B., N.B., C.G., D.K., M.H.P., J.V., K.W. and L.Z. contributed reagents for this study.

Competing interests

Her Majesty the Queen in right of Canada holds a patent on mAbs 2G4, and 4G7, PCT/CA2009/000070, “Monoclonal antibodies for Ebola and Marburg viruses.” K.W. and L.Z. are the owners of Mapp Biopharmaceutical Inc. The authors declare no other competing interests.

Corresponding authors

Correspondence to Larry Zeitlin or Gary P. Kobinger.

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DOI

https://doi.org/10.1038/nature13777

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