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Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo

Defang, Gabriel; Luke, Thomas; Wu, Hua; Zhao, Jincun; Channappanavar, Rudragouda; Coleman, Christopher M.; Jiao, Jin An; Matsushita, Hiroaki; Liu, Ye; Postnikova, Elena N.; Ork, Britini L.; Glenn, Gregory; Flyer, David; Raviprakash, Kanakatte; Kochel, Tadeusz; Smith, Gale; Hensley, Lisa E.; Olinger, Gene G.; Kuhn, Jens H.; Holbrook, Michael R.; Johnson, Reed F.; Wang, Jonathan; Perlman, Stanley; Sullivan, Eddie; Nie, Wensheng; Frieman, Matthew B.

Authors

Gabriel Defang

Thomas Luke

Hua Wu

Jincun Zhao

Rudragouda Channappanavar

CHRISTOPHER COLEMAN CHRISTOPHER.COLEMAN@NOTTINGHAM.AC.UK
Assistant Professor of Infection Immunology

Jin An Jiao

Hiroaki Matsushita

Ye Liu

Elena N. Postnikova

Britini L. Ork

Gregory Glenn

David Flyer

Kanakatte Raviprakash

Tadeusz Kochel

Gale Smith

Lisa E. Hensley

Gene G. Olinger

Jens H. Kuhn

Michael R. Holbrook

Reed F. Johnson

Jonathan Wang

Stanley Perlman

Eddie Sullivan

Wensheng Nie

Matthew B. Frieman



Abstract

Copyright 2016 by the American Association for the Advancement of Science; all rights reserved. As of 13 November 2015, 1618 laboratory-confirmed human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, including 579 deaths, had been reported to the World Health Organization. No specific preventive or therapeutic agent of proven value against MERS-CoV is currently available. Public Health England and the International Severe Acute Respiratory and Emerging Infection Consortium identified passive immunotherapy with neutralizing antibodies as a treatment approach that warrants priority study. Two experimental MERS-CoV vaccines were used to vaccinate two groups of transchromosomic (Tc) bovines that were genetically modified to produce large quantities of fully human polyclonal immunoglobulin G (IgG) antibodies. Vaccination with a clade A ?-irradiated whole killed virion vaccine (Jordan strain) or a clade B spike protein nanoparticle vaccine (Al-Hasa strain) resulted in Tc bovine sera with high enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers in vitro. Two purified Tc bovine human IgG immunoglobulins (Tc hIgG), SAB-300 (produced after Jordan strain vaccination) and SAB-301 (produced after Al-Hasa strain vaccination), also had high ELISA and neutralizing antibody titers without antibody- dependent enhancement in vitro. SAB-301 was selected for in vivo and preclinical studies. Administration of single doses of SAB-301 12 hours before or 24 and 48 hours after MERS-CoV infection (Erasmus Medical Center 2012 strain) of Ad5-hDPP4 receptor-transduced mice rapidly resulted in viral lung titers near or below the limit of detection. Tc bovines, combined with the ability to quickly produce Tc hIgG and develop in vitro assays and animal model(s), potentially offer a platform to rapidly produce a therapeutic to prevent and/or treat MERSCoV infection and/or other emerging infectious diseases.

Citation

Defang, G., Luke, T., Wu, H., Zhao, J., Channappanavar, R., Coleman, C. M., …Frieman, M. B. (2016). Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. Science Translational Medicine, 8(326), 326ra21-326ra21. https://doi.org/10.1126/scitranslmed.aaf1061

Journal Article Type Article
Acceptance Date Jan 14, 2016
Online Publication Date Feb 17, 2016
Publication Date Feb 17, 2016
Deposit Date Dec 17, 2019
Journal Science Translational Medicine
Print ISSN 1946-6234
Electronic ISSN 1946-6242
Publisher American Association for the Advancement of Science
Peer Reviewed Peer Reviewed
Volume 8
Issue 326
Pages 326ra21-326ra21
DOI https://doi.org/10.1126/scitranslmed.aaf1061
Public URL https://nottingham-repository.worktribe.com/output/3589958