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

Nature. 2014 Oct 2;514(7520):47-53. doi: 10.1038/nature13777. Epub 2014 Aug 29.

Authors

Xiangguo Qiu¹, Gary Wong², Jonathan Audet², Alexander Bello², Lisa Fernando¹, Judie B Alimonti¹, Hugues Fausther-Bovendo², Haiyan Wei³, Jenna Aviles¹, Ernie Hiatt⁴, Ashley Johnson⁴, Josh Morton⁴, Kelsi Swope⁴, Ognian Bohorov⁵, Natasha Bohorova⁵, Charles Goodman⁵, Do Kim⁵, Michael H Pauly⁵, Jesus Velasco⁵, James Pettitt⁶, Gene G Olinger⁶, Kevin Whaley⁵, Bianli Xu⁷, James E Strong⁸, Larry Zeitlin⁵, Gary P Kobinger⁹

Affiliations

¹ National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
² 1] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada.
³ 1] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Institute of Infectious Disease, Henan Centre for Disease Control and Prevention, Zhengzhou, 450012 Henan, China.
⁴ Kentucky BioProcessing, Owensboro, Kentucky 42301, USA.
⁵ Mapp Biopharmaceutical Inc., San Diego, California 92121, USA.
⁶ 1] United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland 21702, USA [2] Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland 21702, USA.
⁷ Institute of Infectious Disease, Henan Centre for Disease Control and Prevention, Zhengzhou, 450012 Henan, China.
⁸ 1] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada [3] Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba R3A 1S1, Canada.
⁹ 1] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada [3] Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada [4] Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Amino Acid Sequence
Animals
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / therapeutic use*
Antibodies, Neutralizing / immunology
Antibodies, Neutralizing / therapeutic use
Antibodies, Viral / immunology
Antibodies, Viral / therapeutic use*
Cross Reactions / immunology
Ebolavirus / immunology
Enzyme-Linked Immunosorbent Assay
Female
Guinea
Guinea Pigs
Hemorrhagic Fever, Ebola / blood
Hemorrhagic Fever, Ebola / drug therapy*
Hemorrhagic Fever, Ebola / immunology
Hemorrhagic Fever, Ebola / virology
Immunization, Passive*
Macaca mulatta / immunology
Macaca mulatta / virology
Male
Molecular Sequence Data
Sequence Alignment
Viral Envelope Proteins / chemistry
Viral Envelope Proteins / immunology
Viremia / drug therapy
Viremia / immunology
Viremia / virology

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Viral Envelope Proteins
ZMapp
envelope glycoprotein, Ebola virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding