Fully Human Immunoglobulin G from Transchromosomic Bovines Treats Nonhuman Primates Infected with Ebola Virus Makona Isolate

Thomas Luke, Richard S. Bennett, Dawn M. Gerhardt, Tracey Burdette, Elena Postnikova, Steven Mazur, Anna N. Honko, Nicholas Oberlander, Russell Byrum, Dan Ragland, Marisa St Claire, Krisztina B. Janosko, Gale Smith, Gregory Glenn, Jay Hooper, John Dye, Subhamoy Pal, Kimberly A. Bishop-Lilly, Theron Hamilton, Kenneth FreyLaura Bollinger, Jiro Wada, Hua Wu, Jin An Jiao, Gene G. Olinger, Bronwyn Gunn, Galit Alter, Surender Khurana, Lisa E. Hensley, Eddie Sullivan, Peter B. Jahrling

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Transchromosomic bovines (Tc-bovines) adaptively produce fully human polyclonal immunoglobulin (Ig)G antibodies after exposure to immunogenic antigen(s). The National Interagency Confederation for Biological Research and collaborators rapidly produced and then evaluated anti-Ebola virus IgG immunoglobulins (collectively termed SAB-139) purified from Tc-bovine plasma after sequential hyperimmunization with an Ebola virus Makona isolate glycoprotein nanoparticle vaccine. SAB-139 was characterized by several in vitro production, research, and clinical level assays using wild-type Makona-C05 or recombinant virus/antigens from different Ebola virus variants. SAB-139 potently activates natural killer cells, monocytes, and peripheral blood mononuclear cells and has high-binding avidity demonstrated by surface plasmon resonance. SAB-139 has similar concentrations of galactose-1,3-galactose carbohydrates compared with human-derived intravenous Ig, and the IgG1 subclass antibody is predominant. All rhesus macaques infected with Ebola virus/H.sapiens-tc/GIN/2014/Makona-C05 and treated with sufficient SAB-139 at 1 day (n = 6) or 3 days (n = 6) postinfection survived versus 0% of controls. This study demonstrates that Tc-bovines can produce pathogen-specific human Ig to prevent and/or treat patients when an emerging infectious disease either threatens to or becomes an epidemic.

Original languageEnglish (US)
Pages (from-to)S636-S648
JournalJournal of Infectious Diseases
Volume218
DOIs
StatePublished - Nov 22 2018
Externally publishedYes

Keywords

  • bovine
  • countermeasure
  • Ebola
  • rhesus
  • therapeutic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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