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.
authors.affiliation: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Qiu
authors.affiliation: 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.
authors.forename: Gary
authors.initials: G
authors.lastname: Wong
authors.affiliation: 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.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Audet
authors.affiliation: 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.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bello
authors.affiliation: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Fernando
authors.affiliation: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Judie B
authors.initials: JB
authors.lastname: Alimonti
authors.affiliation: 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.
authors.forename: Hugues
authors.initials: H
authors.lastname: Fausther-Bovendo
authors.affiliation: 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.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wei
authors.affiliation: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Jenna
authors.initials: J
authors.lastname: Aviles
authors.affiliation: Kentucky BioProcessing, Owensboro, Kentucky 42301, USA.
authors.forename: Ernie
authors.initials: E
authors.lastname: Hiatt
authors.affiliation: Kentucky BioProcessing, Owensboro, Kentucky 42301, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Johnson
authors.affiliation: Kentucky BioProcessing, Owensboro, Kentucky 42301, USA.
authors.forename: Josh
authors.initials: J
authors.lastname: Morton
authors.affiliation: Kentucky BioProcessing, Owensboro, Kentucky 42301, USA.
authors.forename: Kelsi
authors.initials: K
authors.lastname: Swope
authors.affiliation: Mapp Biopharmaceutical Inc., San Diego, California 92121, USA.
authors.forename: Ognian
authors.initials: O
authors.lastname: Bohorov
authors.affiliation: Mapp Biopharmaceutical Inc., San Diego, California 92121, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Bohorova
authors.affiliation: Mapp Biopharmaceutical Inc., San Diego, California 92121, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Goodman
authors.affiliation: Mapp Biopharmaceutical Inc., San Diego, California 92121, USA.
authors.forename: Do
authors.initials: D
authors.lastname: Kim
authors.affiliation: Mapp Biopharmaceutical Inc., San Diego, California 92121, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Pauly
authors.affiliation: Mapp Biopharmaceutical Inc., San Diego, California 92121, USA.
authors.forename: Jesus
authors.initials: J
authors.lastname: Velasco
authors.affiliation: 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.
authors.forename: James
authors.initials: J
authors.lastname: Pettitt
authors.affiliation: 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.
authors.forename: Gene G
authors.initials: GG
authors.lastname: Olinger
authors.affiliation: Mapp Biopharmaceutical Inc., San Diego, California 92121, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Whaley
authors.affiliation: Institute of Infectious Disease, Henan Centre for Disease Control and Prevention, Zhengzhou, 450012 Henan, China.
authors.forename: Bianli
authors.initials: B
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: James E
authors.initials: JE
authors.lastname: Strong
authors.affiliation: Mapp Biopharmaceutical Inc., San Diego, California 92121, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Zeitlin
authors.affiliation: 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.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000276:immunology / Q000627:therapeutic use*; D003429:Cross Reactions / Q000276:immunology; D029043:Ebolavirus / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016701:Guinea; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D007116:Immunization, Passive; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000821:virology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; C000594176:ZMapp; C113189:envelope glycoprotein, Ebola virus