Production of Potent Fully Human Polyclonal Antibodies Against Zaire Ebola Virus in Transchromosomal Cattle
USAMRIID Frederick United States
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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 rapidly produce fully human immunoglobulins in substantial quantities against a variety of disease targets. In this study, two Tc bovine expressing high levels of 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 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 mgkg to BALBc mice one day after lethal challenge with maEBOV resulted in 90 protection whereas, 100 the control animals succumbed. The results show that hyperimmunization of Tc bovines with EBOV GP can elicit potent neutralizing and protective human IgG antibodies rapidly and in large quantities.