Journal article
Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo
Science translational medicine, Vol.8(326), pp.326ra21-326ra21
02/17/2016
DOI: 10.1126/scitranslmed.aaf1061
PMID: 26888429
Abstract
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.
Details
- Title: Subtitle
- Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo
- Creators
- Thomas Luke - Viral and Rickettsial Diseases Department, Navy Medical Research Center, The Henry Jackson Foundation for the Advancement of Military Medicine, Silver Spring, MD 20910, USA. thomas.c.luke.ctr@mail.milHua Wu - SAB Biotherapeutics Inc., Sioux Falls, SD 57104, USAJincun Zhao - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, ChinaRudragouda Channappanavar - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USAChristopher M Coleman - Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD 21201, USAJin-An Jiao - SAB Biotherapeutics Inc., Sioux Falls, SD 57104, USAHiroaki Matsushita - SAB Biotherapeutics Inc., Sioux Falls, SD 57104, USAYe Liu - Novavax Inc., Gaithersburg, MD 20878, USAElena N Postnikova - Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USABritini L Ork - Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USAGregory Glenn - Novavax Inc., Gaithersburg, MD 20878, USADavid Flyer - Novavax Inc., Gaithersburg, MD 20878, USAGabriel Defang - Department of Virology, Naval Medical Research Unit-3, Cairo FPO AP 09835, EgyptKanakatte Raviprakash - Department of Virology, Naval Medical Research Unit-3, Cairo FPO AP 09835, EgyptTadeusz Kochel - Viral and Rickettsial Diseases Department, Navy Medical Research Center, Silver Spring, MD 20910, USA. thomas.c.luke.ctr@mail.milJonathan Wang - Thermo Fisher Scientific, South San Francisco, CA 94080, USAWensheng Nie - Thermo Fisher Scientific, South San Francisco, CA 94080, USAGale Smith - Novavax Inc., Gaithersburg, MD 20878, USALisa E Hensley - Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USAGene G Olinger - Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USAJens H Kuhn - Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USAMichael R Holbrook - Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USAReed F Johnson - Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USAStanley Perlman - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USAEddie Sullivan - SAB Biotherapeutics Inc., Sioux Falls, SD 57104, USAMatthew B Frieman - Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA
- Resource Type
- Journal article
- Publication Details
- Science translational medicine, Vol.8(326), pp.326ra21-326ra21
- DOI
- 10.1126/scitranslmed.aaf1061
- PMID
- 26888429
- NLM abbreviation
- Sci Transl Med
- ISSN
- 1946-6242
- eISSN
- 1946-6242
- Publisher
- United States
- Grant note
- Funding:This work was supported in part by the Global Emerging Infections Surveillance Response System (GEIS) funds work unit#847705.82000.25GB.E0018. This project has been funded in part by a supplement to NIH RO1AI095569 (M.B.F.), PO1 AI060699, and RO1 AI091322 (S.P.). The work was supported in part by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases(NIAID), the Integrated Research Facility (NIAID, Division of Clinical Research), and Battelle MemorialRESEARCH ARTICLE www.ScienceTranslationalMedicine.org 17 February 2016 Vol 8 Issue 326 326ra218 Institute’s prime contract with NIAID (contract HHSN272200700016I). B.L.O. and M.R.H. performed this work as employees of Battelle Memorial Institute. Subcontractors to Battelle Memorial Institute who performed this work are as follows: J.H.K. and E.N.P., as employees of Tunnell GovernmentServicesInc.,andG.G.O.,asanemployeeofMRIGlobal.This project was supported in part by the Viral and Rickettsial Diseases Department of the Naval Medical Research Center and The HenryJackson Foundation for the Advancement of Military Medicine contract with the U.S. Navy(contract Omnibus III DO-0005).
- Language
- English
- Date published
- 02/17/2016
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9983777354102771
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