Development of a Cost-effective Ovine Polyclonal Antibody-Based Product, EBOTAb, to Treat Ebola Virus Infection

• Published in: The Journal of infectious diseases Vol. 213; no. 7; pp. 1124 - 1133
• Main Authors: Dowall, Stuart David, Callan, Jo, Zeltina, Antra, Al-Abdulla, Ibrahim, Strecker, Thomas, Fehling, Sarah K., Krähling, Verena, Bosworth, Andrew, Rayner, Emma, Taylor, Irene, Charlton, Sue, Landon, John, Cameron, Ian, Hewson, Roger, Nasidi, Abdulsalami, Bowden, Thomas A., Carroll, Miles W.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.04.2016
• Subjects: Animals; Antibodies, Viral - economics; Antibodies, Viral - therapeutic use; Cost-Benefit Analysis; Ebola virus; Ebolavirus - immunology; Ebolavirus - physiology; Female; Gene Expression Regulation, Viral; Glycoproteins - immunology; Guinea Pigs; HEK293 Cells; Hemorrhagic Fever, Ebola - economics; Hemorrhagic Fever, Ebola - therapy; Humans; Immunoglobulin G - economics; Immunoglobulin G - therapeutic use; Major and Brief Reports; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Protein Binding; Protein Structure, Tertiary; Sheep; Viral Load; VIRUSES; therapeutic; antibody; Ebola; neutralization; efficacy
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiv565

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.