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

Thomas Luke, Hua Wu, Jincun Zhao, Rudragouda Channappanavar, Christopher M. Coleman, Jin An Jiao, Hiroaki Matsushita, Ye Liu, Elena N. Postnikova, Britini L. Ork, Gregory Glenn, David Flyer, Gabriel Defang, Kanakatte Raviprakash, Tadeusz Kochel, Jonathan Wang, Wensheng Nie, Gale Smith, Lisa E. Hensley, Gene G. Olinger & 6 others Jens H. Kuhn, Michael R. Holbrook, Reed F. Johnson, Stanley Perlman, Eddie Sullivan, Matthew B. Frieman

Research output: Contribution to journalArticle

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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 MERSCoV infection and/or other emerging infectious diseases.

Original languageEnglish (US)
Article number326ra21
JournalScience Translational Medicine
Volume8
Issue number326
DOIs
StatePublished - Feb 17 2016

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Immunoglobulin G
Neutralizing Antibodies
Coronavirus Infections
Jordan
Vaccination
Antibody-Dependent Enhancement
Vaccines
Enzyme-Linked Immunosorbent Assay
Emerging Communicable Diseases
Inactivated Vaccines
Passive Immunization
Respiratory Tract Infections
England
Virion
Nanoparticles
Limit of Detection
Immunoglobulins
Therapeutics
Animal Models
Public Health

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. / 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; Defang, Gabriel; Raviprakash, Kanakatte; Kochel, Tadeusz; Wang, Jonathan; Nie, Wensheng; Smith, Gale; Hensley, Lisa E.; Olinger, Gene G.; Kuhn, Jens H.; Holbrook, Michael R.; Johnson, Reed F.; Perlman, Stanley; Sullivan, Eddie; Frieman, Matthew B.

In: Science Translational Medicine, Vol. 8, No. 326, 326ra21, 17.02.2016.

Research output: Contribution to journalArticle

Luke, T, Wu, H, Zhao, J, Channappanavar, R, Coleman, CM, Jiao, JA, Matsushita, H, Liu, Y, Postnikova, EN, Ork, BL, Glenn, G, Flyer, D, Defang, G, Raviprakash, K, Kochel, T, Wang, J, Nie, W, Smith, G, Hensley, LE, Olinger, GG, Kuhn, JH, Holbrook, MR, Johnson, RF, Perlman, S, Sullivan, E & Frieman, MB 2016, 'Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo', Science Translational Medicine, vol. 8, no. 326, 326ra21. https://doi.org/10.1126/scitranslmed.aaf1061
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 ; Defang, Gabriel ; Raviprakash, Kanakatte ; Kochel, Tadeusz ; Wang, Jonathan ; Nie, Wensheng ; Smith, Gale ; Hensley, Lisa E. ; Olinger, Gene G. ; Kuhn, Jens H. ; Holbrook, Michael R. ; Johnson, Reed F. ; Perlman, Stanley ; Sullivan, Eddie ; Frieman, Matthew B. / Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. In: Science Translational Medicine. 2016 ; Vol. 8, No. 326.
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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 MERSCoV infection and/or other emerging infectious diseases.",
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AU - Luke, Thomas

AU - Wu, Hua

AU - Zhao, Jincun

AU - Channappanavar, Rudragouda

AU - Coleman, Christopher M.

AU - Jiao, Jin An

AU - Matsushita, Hiroaki

AU - Liu, Ye

AU - Postnikova, Elena N.

AU - Ork, Britini L.

AU - Glenn, Gregory

AU - Flyer, David

AU - Defang, Gabriel

AU - Raviprakash, Kanakatte

AU - Kochel, Tadeusz

AU - Wang, Jonathan

AU - Nie, Wensheng

AU - Smith, Gale

AU - Hensley, Lisa E.

AU - Olinger, Gene G.

AU - Kuhn, Jens H.

AU - Holbrook, Michael R.

AU - Johnson, Reed F.

AU - Perlman, Stanley

AU - Sullivan, Eddie

AU - Frieman, Matthew B.

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N2 - 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 MERSCoV infection and/or other emerging infectious diseases.

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