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

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)
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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 languageEnglish
Article number24897
Pages (from-to)1-9
Number of pages9
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 25 Apr 2016
Externally publishedYes

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