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

J Infect Dis. 2016 Apr 1;213(7):1124-33. doi: 10.1093/infdis/jiv565. Epub 2015 Dec 28.

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.

Keywords: Ebola; antibody; efficacy; neutralization; therapeutic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / economics
  • Antibodies, Viral / therapeutic use*
  • Cost-Benefit Analysis
  • 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*
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Sheep
  • Viral Load

Substances

  • Antibodies, Viral
  • Glycoproteins
  • Immunoglobulin G
  • Membrane Glycoproteins