[Source: Science Translational Medicine, full page: (LINK). Abstract, edited.]
Research Article / Infectious Disease
Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo [ ]
Thomas Luke 1*, Hua Wu 2, Jincun Zhao 3,4, Rudragouda Channappanavar 3, Christopher M. Coleman 5, Jin-An Jiao 2, Hiroaki Matsushita 2, Ye Liu 6, Elena N. Postnikova 7, Britini L. Ork 7, Gregory Glenn 6, David Flyer 6, Gabriel Defang 8, Kanakatte Raviprakash 9, Tadeusz Kochel 9†, Jonathan Wang 10, Wensheng Nie 10, Gale Smith 6, Lisa E. Hensley 7, Gene G. Olinger 7, Jens H. Kuhn 7, Michael R. Holbrook 7, Reed F. Johnson 11, Stanley Perlman 3, Eddie Sullivan 2 and Matthew B. Frieman 5
Author Affiliations: 1Viral and Rickettsial Diseases Department, Navy Medical Research Center, The Henry Jackson Foundation for the Advancement of Military Medicine, Silver Spring, MD 20910, USA. 2SAB Biotherapeutics Inc., Sioux Falls, SD 57104, USA. 3Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. 4State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China. 5Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA. 6Novavax Inc., Gaithersburg, MD 20878, USA. 7Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA. 8Department of Virology, Naval Medical Research Unit-3, Cairo FPO AP 09835, Egypt. 9Viral and Rickettsial Diseases Department, Navy Medical Research Center, Silver Spring, MD 20910, USA. 10Thermo Fisher Scientific, South San Francisco, CA 94080, USA. 11Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
*Corresponding author. E-mail: email@example.com
† Present address: Forensic Virology, National Biodefense Analysis and Countermeasures Center, Frederick, MD 21702, USA.
Science Translational Medicine 17 Feb 2016: Vol. 8, Issue 326, pp. 326ra21 / DOI: 10.1126/scitranslmed.aaf1061
The ability to treat emerging infections, such as the Middle East respiratory syndrome coronavirus (MERS-CoV), has been limited by the turnaround time of developing new therapeutics. Now, Luke et al. report that transchromosomal bovines can rapidly produce large quantities of fully human polyclonal IgG antibodies to MERS-CoV after vaccination. These antibodies could neutralize MERS-CoV both in vitro and clear infection in mice in vivo. Human testing will confirm whether passive immunization with these antibodies can safely and effectively treat infection in infected individuals.
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 γ-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 MERS-CoV infection and/or other emerging infectious diseases.
Copyright © 2016, American Association for the Advancement of Science
Keywords: Research; Abstracts; MERS-CoV; Serotherapy.