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Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

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

in Animals / Antibodies, Viral - therapeutic use / Cattle / Chlorocebus aethiops / Ebolavirus - immunology / Female / Hemorrhagic Fever, Ebola - drug therapy / Humans / Immunoglobulin G - therapeutic use / Macaca mulatta / Male / Supplement / Vero Cells

2018

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Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

2018

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Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

2018

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Journal Article

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

Janosko, Krisztina B,

Bishop-Lilly, Kimberly A,

Wu, Hua,

Dye, John,

Hensley, Lisa E,

Honko, Anna N,

Hooper, Jay,

Pal, Subhamoy,

Glenn, Gregory,

Smith, Gale,

Hamilton, Theron,

Alter, Galit,

Frey, Kenneth,

Mazur, Steven,

Byrum, Russell,

Khurana, Surender,

Jahrling, Peter B,

Ragland, Dan,

Wada, Jiro,

Sullivan, Eddie,

Gunn, Bronwyn,

Bollinger, Laura,

Luke, Thomas,

Jiao, Jin-an,

Bennett, Richard S,

Oberlander, Nicholas,

Burdette, Tracey,

Olinger, Gene G,

Postnikova, Elena,

Gerhardt, Dawn M,

St. Claire, Marisa

2018

Overview

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-α-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.

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Publisher

Oxford University Press

Subject

Animals

/ Antibodies, Viral - therapeutic use

/ Cattle

/ Chlorocebus aethiops

/ Ebolavirus - immunology

/ Female

/ Hemorrhagic Fever, Ebola - drug therapy