title: Two-mAb cocktail protects macaques against the Makona variant of Ebola virus.
abstract: The 2014-2015 Ebola virus (EBOV) outbreak in West Africa highlighted the urgent need for specific therapeutic interventions for infected patients. The human-mouse chimeric monoclonal antibody (mAb) cocktail ZMapp, previously shown to be efficacious in EBOV (variant Kikwit) lethally infected nonhuman primates (NHPs) when administration was initiated up to 5 days, was used in some patients during the outbreak. We show that a two-antibody cocktail, MIL77E, is fully protective in NHPs when administered at 50 mg/kg 3 days after challenge with a lethal dose of EBOV variant Makona, the virus responsible for the ongoing 2014-2015 outbreak, whereas a similar formulation of ZMapp protected two of three NHPs. The chimeric MIL77E mAb cocktail is produced in engineered Chinese hamster ovary cells and is based on mAbs c13C6 and c2G4 from ZMapp. The use of only two antibodies in MIL77E opens the door to a pan-ebolavirus cocktail.
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada. National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada. xiangguo.qiu@phac-aspc.gc.ca gary.kobinger@phac-aspc.gc.ca fengjiannan77@qq.com zhangby@mab-works.com.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Audet
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Taiping Road #27, Beijing 100850, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lv
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada. National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Shihua
authors.initials: S
authors.lastname: He
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Wong
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada. Institute of Infectious Disease, Henan Center for Disease Control and Prevention, Zhengzhou, Henan 450012, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wei
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Taiping Road #27, Beijing 100850, China.
authors.forename: Longlong
authors.initials: L
authors.lastname: Luo
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Fernando
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada. National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kroeker
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Hugues
authors.initials: H
authors.lastname: Fausther Bovendo
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bello
authors.affiliation: Beijing Mabworks Biotech Co. Ltd., No. 99, Kechuang 14th Street, Economic-Technological Development Area, Beijing 101111, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Beijing Mabworks Biotech Co. Ltd., No. 99, Kechuang 14th Street, Economic-Technological Development Area, Beijing 101111, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Ye
authors.affiliation: Royal Free London NHS (National Health Service) Foundation Trust, Pond Street, London NW3 2QG, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Jacobs
authors.affiliation: National Institute for Infectious Diseases "Lazzaro Spallanzani," Rome 00149, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Erica Ollmann
authors.initials: EO
authors.lastname: Saphire
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Bi
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Taiping Road #27, Beijing 100850, China.
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.affiliation: Mapp Biopharmaceutical Inc., San Diego, CA 92121, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Zeitlin
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Taiping Road #27, Beijing 100850, China. xiangguo.qiu@phac-aspc.gc.ca gary.kobinger@phac-aspc.gc.ca fengjiannan77@qq.com zhangby@mab-works.com.
authors.forename: Jiannan
authors.initials: J
authors.lastname: Feng
authors.affiliation: Beijing Mabworks Biotech Co. Ltd., No. 99, Kechuang 14th Street, Economic-Technological Development Area, Beijing 101111, China. xiangguo.qiu@phac-aspc.gc.ca gary.kobinger@phac-aspc.gc.ca fengjiannan77@qq.com zhangby@mab-works.com.
authors.forename: Boyan
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada. National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada. Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104-4238, USA. xiangguo.qiu@phac-aspc.gc.ca gary.kobinger@phac-aspc.gc.ca fengjiannan77@qq.com zhangby@mab-works.com.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016466:CHO Cells; D002853:Chromatography, Liquid; D006224:Cricetinae; D003412:Cricetulus; D029043:Ebolavirus / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy* / Q000517:prevention & control*; D008251:Macaca; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase