Post-exposure treatment of non-human primates lethally infected with Ebola virus with EBOTAb, a purified ovine IgG product

Sci Rep. 2017 Jun 22;7(1):4099. doi: 10.1038/s41598-017-03910-7.

Abstract

Despite sporadic outbreaks of Ebola virus (EBOV) over the last 4 decades and the recent public health emergency in West Africa, there are still no approved vaccines or therapeutics for the treatment of acute EBOV disease (EVD). In response to the 2014 outbreak, an ovine immunoglobulin therapy was developed, termed EBOTAb. After promising results in the guinea pig model of EBOV infection, EBOTAb was tested in the cynomolgus macaque non-human primate model of lethal EBOV infection. To ensure stringent therapeutic testing conditions to replicate likely clinical usage, EBOTAb was first delivered 1, 2 or 3 days post-challenge with a lethal dose of EBOV. Results showed a protective effect of EBOTAb given post-exposurally, with survival rates decreasing with increasing time after challenge. Viremia results demonstrated that EBOTAb resulted in a decreased circulation of EBOV in the bloodstream. Additionally, assay of liver enzymes and histology analysis of local tissues identified differences between EBOTAb-treated and untreated groups. The results presented demonstrate that EBOTAb conferred protection against EBOV when given post-exposure and should be explored and developed further as a potential intervention strategy for future outbreaks, which are likely to occur.

MeSH terms

  • Animals
  • Antibodies, Viral / pharmacology*
  • Biomarkers
  • Disease Models, Animal
  • Ebolavirus / genetics
  • Ebolavirus / immunology*
  • Hemorrhagic Fever, Ebola / drug therapy*
  • Hemorrhagic Fever, Ebola / immunology*
  • Hemorrhagic Fever, Ebola / mortality
  • Hemorrhagic Fever, Ebola / virology
  • Immunoglobulin G / pharmacology*
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver / metabolism
  • Liver / pathology
  • Liver / virology
  • Macaca fascicularis
  • Male
  • Post-Exposure Prophylaxis
  • Primates
  • RNA, Viral
  • Time Factors
  • Treatment Outcome
  • Viral Load

Substances

  • Antibodies, Viral
  • Biomarkers
  • Immunoglobulin G
  • RNA, Viral