title: Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo.
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.
authors.affiliation: 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.mil.
authors.forename: Thomas
authors.initials: T
authors.lastname: Luke
authors.affiliation: SAB Biotherapeutics Inc., Sioux Falls, SD 57104, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
authors.affiliation: 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, China.
authors.forename: Jincun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Rudragouda
authors.initials: R
authors.lastname: Channappanavar
authors.affiliation: Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Coleman
authors.affiliation: SAB Biotherapeutics Inc., Sioux Falls, SD 57104, USA.
authors.forename: Jin-An
authors.initials: JA
authors.lastname: Jiao
authors.affiliation: SAB Biotherapeutics Inc., Sioux Falls, SD 57104, USA.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsushita
authors.affiliation: Novavax Inc., Gaithersburg, MD 20878, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Elena N
authors.initials: EN
authors.lastname: Postnikova
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Britini L
authors.initials: BL
authors.lastname: Ork
authors.affiliation: Novavax Inc., Gaithersburg, MD 20878, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Glenn
authors.affiliation: Novavax Inc., Gaithersburg, MD 20878, USA.
authors.forename: David
authors.initials: D
authors.lastname: Flyer
authors.affiliation: Department of Virology, Naval Medical Research Unit-3, Cairo FPO AP 09835, Egypt.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Defang
authors.affiliation: Department of Virology, Naval Medical Research Unit-3, Cairo FPO AP 09835, Egypt.
authors.forename: Kanakatte
authors.initials: K
authors.lastname: Raviprakash
authors.affiliation: Viral and Rickettsial Diseases Department, Navy Medical Research Center, Silver Spring, MD 20910, USA. thomas.c.luke.ctr@mail.mil.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Kochel
authors.affiliation: Thermo Fisher Scientific, South San Francisco, CA 94080, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Thermo Fisher Scientific, South San Francisco, CA 94080, USA.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Nie
authors.affiliation: Novavax Inc., Gaithersburg, MD 20878, USA.
authors.forename: Gale
authors.initials: G
authors.lastname: Smith
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Gene G
authors.initials: GG
authors.lastname: Olinger
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Jens H
authors.initials: JH
authors.lastname: Kuhn
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Holbrook
authors.affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Reed F
authors.initials: RF
authors.lastname: Johnson
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Perlman
authors.affiliation: SAB Biotherapeutics Inc., Sioux Falls, SD 57104, USA.
authors.forename: Eddie
authors.initials: E
authors.lastname: Sullivan
authors.affiliation: Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Frieman
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D019067:Antibody-Dependent Enhancement; D002417:Cattle; D033481:Chromosomes, Mammalian / Q000235:genetics*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008807:Mice, Inbred BALB C; D065207:Middle East Respiratory Syndrome Coronavirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D014611:Vaccination; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D007074:Immunoglobulin G; D012333:RNA, Messenger; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4