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 Frey; Laura 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

doi:10.1093/infdis/jiy377

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 journal › Article › peer-review

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 language	English (US)
Pages (from-to)	S636-S648
Journal	Journal of Infectious Diseases
Volume	218
DOIs	https://doi.org/10.1093/infdis/jiy377
State	Published - Nov 22 2018
Externally published	Yes

Keywords

bovine
countermeasure
Ebola
rhesus
therapeutic

ASJC Scopus subject areas

Immunology and Allergy
Infectious Diseases

Access to Document

10.1093/infdis/jiy377

Cite this

Luke, T., Bennett, R. S., Gerhardt, D. M., Burdette, T., Postnikova, E., Mazur, S., Honko, A. N., Oberlander, N., Byrum, R., Ragland, D., St Claire, M., Janosko, K. B., Smith, G., Glenn, G., Hooper, J., Dye, J., Pal, S., Bishop-Lilly, K. A., Hamilton, T., ... Jahrling, P. B. (2018). Fully Human Immunoglobulin G from Transchromosomic Bovines Treats Nonhuman Primates Infected with Ebola Virus Makona Isolate. Journal of Infectious Diseases, 218, S636-S648. https://doi.org/10.1093/infdis/jiy377

Luke, T, Bennett, RS, Gerhardt, DM, Burdette, T, Postnikova, E, Mazur, S, Honko, AN, Oberlander, N, Byrum, R, Ragland, D, St Claire, M, Janosko, KB, Smith, G, Glenn, G, Hooper, J, Dye, J, Pal, S, Bishop-Lilly, KA, Hamilton, T, Frey, K, Bollinger, L, Wada, J, Wu, H, Jiao, JA, Olinger, GG, Gunn, B, Alter, G, Khurana, S, Hensley, LE, Sullivan, E & Jahrling, PB 2018, 'Fully Human Immunoglobulin G from Transchromosomic Bovines Treats Nonhuman Primates Infected with Ebola Virus Makona Isolate', Journal of Infectious Diseases, vol. 218, pp. S636-S648. https://doi.org/10.1093/infdis/jiy377

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

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.",

keywords = "bovine, countermeasure, Ebola, rhesus, therapeutic",

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

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AU - Bennett, Richard S.

AU - Gerhardt, Dawn M.

AU - Burdette, Tracey

AU - Postnikova, Elena

AU - Mazur, Steven

AU - Honko, Anna N.

AU - Oberlander, Nicholas

AU - Byrum, Russell

AU - Ragland, Dan

AU - St Claire, Marisa

AU - Janosko, Krisztina B.

AU - Smith, Gale

AU - Glenn, Gregory

AU - Hooper, Jay

AU - Dye, John

AU - Pal, Subhamoy

AU - Bishop-Lilly, Kimberly A.

AU - Hamilton, Theron

AU - Frey, Kenneth

AU - Bollinger, Laura

AU - Wada, Jiro

AU - Wu, Hua

AU - Jiao, Jin An

AU - Olinger, Gene G.

AU - Gunn, Bronwyn

AU - Alter, Galit

AU - Khurana, Surender

AU - Hensley, Lisa E.

AU - Sullivan, Eddie

AU - Jahrling, Peter B.

PY - 2018/11/22

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AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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