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.
Highlights
In laboratory studies, treatment with multiple doses of KZ52, a human monoclonal antibody (Mab) derived from an EBOV survivor, prevented Ebola virus disease (EVD) in guinea pigs[6]; follow up studies in Georgia, 30602, USA
Previous studies using a codon-optimized DNA vaccine expressing the EBOV GP gene showed that protective antibodies were generated and complete protection was observed in mice and monkeys challenged by EBOV28
We hyperimmunized two Tc bovines that expressed high levels of fully human IgG22 with a vaccine comprised of EBOV/Makona recombinant GP (rGP) nanoparticles and SAB’s proprietary adjuvant
Summary
Treatment with multiple doses of KZ52, a human monoclonal antibody (Mab) derived from an EBOV survivor, prevented Ebola virus disease (EVD) in guinea pigs[6]; follow up studies in Georgia, 30602, USA. Convalescent plasma and ZMapp have been used in a small number of humans with EBOV infection, but logistical and production limitations have prevented widespread use[12,13,14] Current immunoglobulin products, such as human intravenous immunoglobulin (IVIG), monoclonal antibodies, and animal-derived polyclonal antibodies (pAbs), have known limitations. It is clear that an innovative and rapid approach, combining the good safety profile of human polyclonal antibody products with the high neutralizing antibody activity derived from hyperimmune animals, is needed. To address these limitations, SAB Biotherapeutics (SAB) has developed the Transchromosomic (Tc) bovine. The therapeutic efficacy of anti-hantavirus human polyclonal antibody clearly demonstrated the proof-of-concept that it is possible to produce a candidate anti-viral biologic rapidly at high and scalable levels
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