title: The emergence of antibody therapies for Ebola.
abstract: This review describes the history of Ebola monoclonal antibody (mAb) development leading up to the recent severe Ebola outbreak in West Africa. The Ebola virus has presented numerous perplexing challenges in the long effort to develop therapeutic antibody strategies. Since the first report of a neutralizing human anti-Ebola mAb in 1999, the straightforward progression from in vitro neutralization resulting in in vivo protection and therapy has not occurred. A number of mAbs, including the first reported, failed to protect non-human primates (NHPs) in spite of protection in rodents. An appreciation of the role of effector functions to antibody efficacy has contributed significantly to understanding mechanisms of in vivo protection. However a crucial contribution, as measured by post-exposure therapy of NHPs, involved the comprehensive testing of mAb cocktails. This effort was aided by the use of plant production technology where various combinations of mAbs could be rapidly produced and tested. Introduction of appropriate modifications, such as specific glycan profiles, also improved therapeutic efficacy. The resulting cocktail, ZMapp™, consists of three mAbs that were identified from numerous mAb candidates. ZMapp™ \ is now being evaluated in human clinical trials but has already played a role in bringing awareness to the potential of antibody therapy for Ebola.
authors.affiliation: Mapp Biopharmaceutical, Inc. San Diego, CA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hiatt
authors.affiliation: Mapp Biopharmaceutical, Inc. San Diego, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Pauly
authors.affiliation: Mapp Biopharmaceutical, Inc. San Diego, CA, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Whaley
authors.affiliation: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, MB, Canada.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Qiu
authors.affiliation: National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, MB, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Kobinger
authors.affiliation: Mapp Biopharmaceutical, Inc. San Diego, CA, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Zeitlin
mesh_terms: D000354:Africa, Western; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000627:therapeutic use*; D029043:Ebolavirus / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity; D000939:Epitopes / Q000737:chemistry; D006031:Glycosylation; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000401:mortality / Q000628:therapy* / Q000821:virology; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000627:therapeutic use*; D008253:Macaca mulatta; D051379:Mice; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D007074:Immunoglobulin G; D011994:Recombinant Proteins
keywords: Ebola antibody discovery; Ebola virus; effector functions; passive immunotherapy