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Author Notes:

Correspondence and requests for materials should be addressed to J.-a.J. (email: jjiao@sabbiotherapeutics.com)

Conceived of the study: E.J.S., G.S., G.G. and T.C.L.

Designed the experiments: J.-a.J., J.M.D., H.W., J.W.H., S.A.K., E.J.S., T.C.L., G.S., C.Y., R.W.C. and R.A.T.

Performed the experiments: S.A.K., A.I.K., E.M.C., R.A.O., S.F., A.S.H., H.G., R.A.B., J.M.B., S.A.K., C.Y., W.L. and L.Y.

Analyzed the data: J.M.D., H.W., J.W.H., S.A.K., E.J.S., T.C.L., G.S., C.Y., L.Y., R.W.C., R.A.T. and J.-a.J.

Contributed reagents/materials/analysis tools: J.M.D., H.W., J.W.H., S.A.K., E.J.S., G.S., R.W.C., R.A.T. and J.-a.J.

Wrote the paper: J.-a.J., H.W., J.M.D., J.W.H., S.A.K. and G.S.

Competing interests: Authors from SAB Biotherapeutics, Inc. and Novavax, Inc were employees of these for-profit organizations at the time of the study and authors from these organizations have financial interests in their respective companies. The authors also have submitted patent applications related to the work which are pending. The authors have developed a lead candidate therapeutic antibody (SAB-139) from this work, which would be considered a product of the company intended for further development as a commercial venture. This does not alter the authors’ adherence to policies on sharing data and materials.

Financial interest in this work is currently owned by SAB Biotherapeutics, Inc, and Novavax, Inc. who did have a role in the decision to publish as well as the preparation of the manuscript. While it is considered beneficial to the interests of SAB Biotherapeutics, Inc and Novavax, Inc. to publish this work, this consideration played no role in the study design, data collection and analysis and preparation of the manuscript.

The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the U.S. Army or Navy, or Department of Defense. Some of the authors are employees of the U.S. Government, and this work was prepared as part of their official duties.

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Research Funding:

This work was funded in part by SAB Biotherapeutics, Inc and Novavax, Inc.

This project was supported in part by the Viral and Rickettsial Diseases Department of the Naval Medical Research Center (VRDD, NMRC) and The Henry Jackson Foundation for the Advancement of Military Medicine contract with the US Navy (Contract # Omnibus III DO-0005).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • HEMORRHAGIC-FEVER
  • NONHUMAN-PRIMATES
  • INFECTION
  • PROPHYLAXIS
  • PROTECTION
  • DISEASE
  • ZMAPP

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

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Journal Title:

Scientific Reports

Volume:

Volume 6

Publisher:

, Pages 24897-24897

Type of Work:

Article | Final Publisher PDF

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.

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© 2016, Macmillan Publishers Limited

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).

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