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; Gary P. Kobinger

doi:10.1038/nature13777

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 PettittGene G. Olinger, Kevin Whaley, Bianli Xu, James E. Strong, Larry Zeitlin, Gary P. Kobinger

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802 Scopus citations

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.

Original language	English (US)
Pages (from-to)	47-53
Number of pages	7
Journal	Nature
Volume	514
Issue number	7520
DOIs	https://doi.org/10.1038/nature13777
State	Published - Oct 2 2014
Externally published	Yes

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Qiu, X., Wong, G., Audet, J., Bello, A., Fernando, L., Alimonti, J. B., Fausther-Bovendo, H., Wei, H., Aviles, J., Hiatt, E., Johnson, A., Morton, J., Swope, K., Bohorov, O., Bohorova, N., Goodman, C., Kim, D., Pauly, M. H., Velasco, J., ... Kobinger, G. P. (2014). Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature, 514(7520), 47-53. https://doi.org/10.1038/nature13777

Qiu, X, Wong, G, Audet, J, Bello, A, Fernando, L, Alimonti, JB, Fausther-Bovendo, H, Wei, H, Aviles, J, Hiatt, E, Johnson, A, Morton, J, Swope, K, Bohorov, O, Bohorova, N, Goodman, C, Kim, D, Pauly, MH, Velasco, J, Pettitt, J, Olinger, GG, Whaley, K, Xu, B, Strong, JE, Zeitlin, L & Kobinger, GP 2014, 'Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp', Nature, vol. 514, no. 7520, pp. 47-53. https://doi.org/10.1038/nature13777

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title = "Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp",

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.",

author = "Xiangguo Qiu and Gary Wong and Jonathan Audet and Alexander Bello and Lisa Fernando and Alimonti, {Judie B.} and Hugues Fausther-Bovendo and Haiyan Wei and Jenna Aviles and Ernie Hiatt and Ashley Johnson and Josh Morton and Kelsi Swope and Ognian Bohorov and Natasha Bohorova and Charles Goodman and Do Kim and Pauly, {Michael H.} and Jesus Velasco and James Pettitt and Olinger, {Gene G.} and Kevin Whaley and Bianli Xu and Strong, {James E.} and Larry Zeitlin and Kobinger, {Gary P.}",

note = "Funding Information: 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). Publisher Copyright: {\textcopyright}2014 Macmillan Publishers Limited. All rights reserved.",

year = "2014",

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doi = "10.1038/nature13777",

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AU - Qiu, Xiangguo

AU - Wong, Gary

AU - Audet, Jonathan

AU - Bello, Alexander

AU - Fernando, Lisa

AU - Alimonti, Judie B.

AU - Fausther-Bovendo, Hugues

AU - Wei, Haiyan

AU - Aviles, Jenna

AU - Hiatt, Ernie

AU - Johnson, Ashley

AU - Morton, Josh

AU - Swope, Kelsi

AU - Bohorov, Ognian

AU - Bohorova, Natasha

AU - Goodman, Charles

AU - Kim, Do

AU - Pauly, Michael H.

AU - Velasco, Jesus

AU - Pettitt, James

AU - Olinger, Gene G.

AU - Whaley, Kevin

AU - Xu, Bianli

AU - Strong, James E.

AU - Zeitlin, Larry

AU - Kobinger, Gary P.

N1 - Funding Information: 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). Publisher Copyright: ©2014 Macmillan Publishers Limited. All rights reserved.

PY - 2014/10/2

Y1 - 2014/10/2

N2 - 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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Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp

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