Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle

John M. Dye; Hua Wu; Jay W. Hooper; Surender Khurana; Ana I. Kuehne; Elizabeth M. Coyle; Ramon A. Ortiz; Sandra Fuentes; Andrew S. Herbert; Hana Golding; Russell A. Bakken; Jennifer M. Brannan; Steve A. Kwilas; Eddie J. Sullivan; Thomas C. Luke; Gale Smith; Gregory Glenn; Wenfang Li; Ling Ye; Chinglai Yang; Richard W. Compans; Ralph A. Tripp; Jin An Jiao

doi:10.1038/srep24897

Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle

John M. Dye, Hua Wu, Jay W. Hooper, Surender Khurana, Ana I. Kuehne, Elizabeth M. Coyle, Ramon A. Ortiz, Sandra Fuentes, Andrew S. Herbert, Hana Golding, Russell A. Bakken, Jennifer M. Brannan, Steve A. Kwilas, Eddie J. Sullivan, Thomas C. Luke, Gale Smith, Gregory Glenn, Wenfang Li, Ling Ye, Chinglai YangRichard W. Compans, Ralph A. Tripp, Jin An Jiao

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Abstract

Polyclonal antibodies, derived from humans or hyperimmunized animals, have been used prophylactically or therapeutically as countermeasures for a variety of infectious diseases. SAB Biotherapeutics has successfully developed a transchromosomic (Tc) bovine platform technology that can produce fully human immunoglobulins rapidly, and in substantial quantities, against a variety of disease targets. In this study, two Tc bovines expressing high levels of fully human IgG were hyperimmunized with a recombinant glycoprotein (GP) vaccine consisting of the 2014 Ebola virus (EBOV) Makona isolate. Serum collected from these hyperimmunized Tc bovines contained high titers of human IgG against EBOV GP as determined by GP specific ELISA, surface plasmon resonance (SPR), and virus neutralization assays. Fully human polyclonal antibodies against EBOV were purified and evaluated in a mouse challenge model using mouse adapted Ebola virus (maEBOV). Intraperitoneal administration of the purified anti-EBOV IgG (100 mg/kg) to BALB/c mice one day after lethal challenge with maEBOV resulted in 90% protection; whereas 100% of the control animals succumbed. The results show that hyperimmunization of Tc bovines with EBOV GP can elicit protective and potent neutralizing fully human IgG antibodies rapidly and in commercially viable quantities.

Original language	English
Article number	24897
Pages (from-to)	1-9
Number of pages	9
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep24897
Publication status	Published - 25 Apr 2016
Externally published	Yes

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Dye, J. M., Wu, H., Hooper, J. W., Khurana, S., Kuehne, A. I., Coyle, E. M., Ortiz, R. A., Fuentes, S., Herbert, A. S., Golding, H., Bakken, R. A., Brannan, J. M., Kwilas, S. A., Sullivan, E. J., Luke, T. C., Smith, G., Glenn, G., Li, W., Ye, L., ... Jiao, J. A. (2016). Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle. Scientific Reports, 6, 1-9. [24897]. https://doi.org/10.1038/srep24897

@article{66106d5a312046979be3e94856dfd93e,

title = "Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle",

abstract = "Polyclonal antibodies, derived from humans or hyperimmunized animals, have been used prophylactically or therapeutically as countermeasures for a variety of infectious diseases. SAB Biotherapeutics has successfully developed a transchromosomic (Tc) bovine platform technology that can produce fully human immunoglobulins rapidly, and in substantial quantities, against a variety of disease targets. In this study, two Tc bovines expressing high levels of fully human IgG were hyperimmunized with a recombinant glycoprotein (GP) vaccine consisting of the 2014 Ebola virus (EBOV) Makona isolate. Serum collected from these hyperimmunized Tc bovines contained high titers of human IgG against EBOV GP as determined by GP specific ELISA, surface plasmon resonance (SPR), and virus neutralization assays. Fully human polyclonal antibodies against EBOV were purified and evaluated in a mouse challenge model using mouse adapted Ebola virus (maEBOV). Intraperitoneal administration of the purified anti-EBOV IgG (100 mg/kg) to BALB/c mice one day after lethal challenge with maEBOV resulted in 90% protection; whereas 100% of the control animals succumbed. The results show that hyperimmunization of Tc bovines with EBOV GP can elicit protective and potent neutralizing fully human IgG antibodies rapidly and in commercially viable quantities.",

author = "Dye, {John M.} and Hua Wu and Hooper, {Jay W.} and Surender Khurana and Kuehne, {Ana I.} and Coyle, {Elizabeth M.} and Ortiz, {Ramon A.} and Sandra Fuentes and Herbert, {Andrew S.} and Hana Golding and Bakken, {Russell A.} and Brannan, {Jennifer M.} and Kwilas, {Steve A.} and Sullivan, {Eddie J.} and Luke, {Thomas C.} and Gale Smith and Gregory Glenn and Wenfang Li and Ling Ye and Chinglai Yang and Compans, {Richard W.} and Tripp, {Ralph A.} and Jiao, {Jin An}",

year = "2016",

month = apr,

day = "25",

doi = "10.1038/srep24897",

language = "English",

volume = "6",

pages = "1--9",

journal = "Scientific Reports",

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Dye, JM, Wu, H, Hooper, JW, Khurana, S, Kuehne, AI, Coyle, EM, Ortiz, RA, Fuentes, S, Herbert, AS, Golding, H, Bakken, RA, Brannan, JM, Kwilas, SA, Sullivan, EJ, Luke, TC, Smith, G, Glenn, G, Li, W, Ye, L, Yang, C, Compans, RW, Tripp, RA & Jiao, JA 2016, 'Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle', Scientific Reports, vol. 6, 24897, pp. 1-9. https://doi.org/10.1038/srep24897

TY - JOUR

T1 - Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle

AU - Dye, John M.

AU - Wu, Hua

AU - Hooper, Jay W.

AU - Khurana, Surender

AU - Kuehne, Ana I.

AU - Coyle, Elizabeth M.

AU - Ortiz, Ramon A.

AU - Fuentes, Sandra

AU - Herbert, Andrew S.

AU - Golding, Hana

AU - Bakken, Russell A.

AU - Brannan, Jennifer M.

AU - Kwilas, Steve A.

AU - Sullivan, Eddie J.

AU - Luke, Thomas C.

AU - Smith, Gale

AU - Glenn, Gregory

AU - Li, Wenfang

AU - Ye, Ling

AU - Yang, Chinglai

AU - Compans, Richard W.

AU - Tripp, Ralph A.

AU - Jiao, Jin An

PY - 2016/4/25

Y1 - 2016/4/25

N2 - Polyclonal antibodies, derived from humans or hyperimmunized animals, have been used prophylactically or therapeutically as countermeasures for a variety of infectious diseases. SAB Biotherapeutics has successfully developed a transchromosomic (Tc) bovine platform technology that can produce fully human immunoglobulins rapidly, and in substantial quantities, against a variety of disease targets. In this study, two Tc bovines expressing high levels of fully human IgG were hyperimmunized with a recombinant glycoprotein (GP) vaccine consisting of the 2014 Ebola virus (EBOV) Makona isolate. Serum collected from these hyperimmunized Tc bovines contained high titers of human IgG against EBOV GP as determined by GP specific ELISA, surface plasmon resonance (SPR), and virus neutralization assays. Fully human polyclonal antibodies against EBOV were purified and evaluated in a mouse challenge model using mouse adapted Ebola virus (maEBOV). Intraperitoneal administration of the purified anti-EBOV IgG (100 mg/kg) to BALB/c mice one day after lethal challenge with maEBOV resulted in 90% protection; whereas 100% of the control animals succumbed. The results show that hyperimmunization of Tc bovines with EBOV GP can elicit protective and potent neutralizing fully human IgG antibodies rapidly and in commercially viable quantities.

AB - Polyclonal antibodies, derived from humans or hyperimmunized animals, have been used prophylactically or therapeutically as countermeasures for a variety of infectious diseases. SAB Biotherapeutics has successfully developed a transchromosomic (Tc) bovine platform technology that can produce fully human immunoglobulins rapidly, and in substantial quantities, against a variety of disease targets. In this study, two Tc bovines expressing high levels of fully human IgG were hyperimmunized with a recombinant glycoprotein (GP) vaccine consisting of the 2014 Ebola virus (EBOV) Makona isolate. Serum collected from these hyperimmunized Tc bovines contained high titers of human IgG against EBOV GP as determined by GP specific ELISA, surface plasmon resonance (SPR), and virus neutralization assays. Fully human polyclonal antibodies against EBOV were purified and evaluated in a mouse challenge model using mouse adapted Ebola virus (maEBOV). Intraperitoneal administration of the purified anti-EBOV IgG (100 mg/kg) to BALB/c mice one day after lethal challenge with maEBOV resulted in 90% protection; whereas 100% of the control animals succumbed. The results show that hyperimmunization of Tc bovines with EBOV GP can elicit protective and potent neutralizing fully human IgG antibodies rapidly and in commercially viable quantities.

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U2 - 10.1038/srep24897

DO - 10.1038/srep24897

M3 - Article

C2 - 27109916

AN - SCOPUS:84964658344

SN - 2045-2322

VL - 6

SP - 1

EP - 9

JO - Scientific Reports

JF - Scientific Reports

M1 - 24897

ER -

Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle

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