Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo
JournalScience Translational Medicine
PublisherAmerican Association for the Advancement of Science
MetadataShow full item record
AbstractAs 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.
SponsorsHenry M. Jackson Foundation, HJF; National Institute of Allergy and Infectious Diseases, NIAID, U.S. Department of Health and Human Services, HHS: KC776174.1; National Institutes of Health, NIH: RO1 AI095569, RO1 AI091322, PO1 AI060699; Erasmus Medisch Centrum, Erasmus MC: 7074983, 7491867, 14/416870, 7928285, 13/510327, 847705.82000.25GB.E0018, 7803981, 14/056517; U.S. Department of Defense, DOD; Battelle: HHSN272200700016I; U.S. Navy: III DO-0005
polyclonal immunoglobulin G antibodies
Middle East Respiratory Syndrome Coronavirus
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84973153410&doi=10.1126%2fscitranslmed.aaf1061&partnerID=40&md5=412e20538e1071a2eb4e8542d9c7ee07; http://hdl.handle.net/10713/12402
- A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform.
- Authors: Malczyk AH, Kupke A, Prüfer S, Scheuplein VA, Hutzler S, Kreuz D, Beissert T, Bauer S, Hubich-Rau S, Tondera C, Eldin HS, Schmidt J, Vergara-Alert J, Süzer Y, Seifried J, Hanschmann KM, Kalinke U, Herold S, Sahin U, Cichutek K, Waibler Z, Eickmann M, Becker S, Mühlebach MD
- Issue date: 2015 Nov
- Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia.
- Authors: Arabi YM, Hajeer AH, Luke T, Raviprakash K, Balkhy H, Johani S, Al-Dawood A, Al-Qahtani S, Al-Omari A, Al-Hameed F, Hayden FG, Fowler R, Bouchama A, Shindo N, Al-Khairy K, Carson G, Taha Y, Sadat M, Alahmadi M
- Issue date: 2016 Sep
- Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length Spike protein of Middle East respiratory syndrome coronavirus.
- Authors: Kim MH, Kim HJ, Chang J
- Issue date: 2019
- Antibody-mediated protection against MERS-CoV in the murine model.
- Authors: New RRC, Moore BD, Butcher W, Mahood R, Lever MS, Smither S, O'Brien L, Weller SA, Bayliss M, Gibson LCD, Macleod C, Bogus M, Harvey R, Almond N, Williamson ED
- Issue date: 2019 Jul 9
- A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines.
- Authors: Du L, Kou Z, Ma C, Tao X, Wang L, Zhao G, Chen Y, Yu F, Tseng CT, Zhou Y, Jiang S
- Issue date: 2013