title: Development of a Cost-effective Ovine Polyclonal Antibody-Based Product, EBOTAb, to Treat Ebola Virus Infection.
abstract: The highly glycosylated glycoprotein spike of Ebola virus (EBOV-GP1,2) is the primary target of the humoral host response. Recombinant EBOV-GP ectodomain (EBOV-GP1,2ecto) expressed in mammalian cells was used to immunize sheep and elicited a robust immune response and produced high titers of high avidity polyclonal antibodies. Investigation of the neutralizing activity of the ovine antisera in vitro revealed that it neutralized EBOV. A pool of intact ovine immunoglobulin G, herein termed EBOTAb, was prepared from the antisera and used for an in vivo guinea pig study. When EBOTAb was delivered 6 hours after challenge, all animals survived without experiencing fever or other clinical manifestations. In a second series of guinea pig studies, the administration of EBOTAb dosing was delayed for 48 or 72 hours after challenge, resulting in 100% and 75% survival, respectively. These studies illustrate the usefulness of EBOTAb in protecting against EBOV-induced disease.
authors.affiliation: Public Health England, Salisbury.
authors.forename: Stuart David
authors.initials: SD
authors.lastname: Dowall
authors.affiliation: MicroPharm, Newcastle Emlyn.
authors.forename: Jo
authors.initials: J
authors.lastname: Callan
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, United Kingdom.
authors.forename: Antra
authors.initials: A
authors.lastname: Zeltina
authors.affiliation: MicroPharm, Newcastle Emlyn.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Al-Abdulla
authors.affiliation: Institute of Virology, Philipps University Marburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Strecker
authors.affiliation: Institute of Virology, Philipps University Marburg, Germany.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Fehling
authors.affiliation: Institute of Virology, Philipps University Marburg, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Krähling
authors.affiliation: Public Health England, Salisbury.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bosworth
authors.affiliation: Public Health England, Salisbury.
authors.forename: Emma
authors.initials: E
authors.lastname: Rayner
authors.affiliation: Public Health England, Salisbury.
authors.forename: Irene
authors.initials: I
authors.lastname: Taylor
authors.affiliation: Public Health England, Salisbury.
authors.forename: Sue
authors.initials: S
authors.lastname: Charlton
authors.affiliation: MicroPharm, Newcastle Emlyn.
authors.forename: John
authors.initials: J
authors.lastname: Landon
authors.affiliation: MicroPharm, Newcastle Emlyn.
authors.forename: Ian
authors.initials: I
authors.lastname: Cameron
authors.affiliation: Public Health England, Salisbury.
authors.forename: Roger
authors.initials: R
authors.lastname: Hewson
authors.affiliation: Nigerian Centre for Disease Control, Abuja.
authors.forename: Abdulsalami
authors.initials: A
authors.lastname: Nasidi
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, United Kingdom.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bowden
authors.affiliation: Public Health England, Salisbury.
authors.forename: Miles W
authors.initials: MW
authors.lastname: Carroll
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D029043:Ebolavirus / Q000276:immunology / Q000502:physiology*; D005260:Female; D015967:Gene Expression Regulation, Viral; D006023:Glycoproteins / Q000276:immunology*; D006168:Guinea Pigs; D057809:HEK293 Cells; D019142:Hemorrhagic Fever, Ebola / Q000191:economics / Q000628:therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000191:economics / Q000627:therapeutic use*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012756:Sheep; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D006023:Glycoproteins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins
keywords: Ebola; antibody; efficacy; neutralization; therapeutic