(C) Viral load in extra-respiratory tissues from marmosets 7 dpi. m336 or hyperimmune plasma reduced signs of clinical disease. ? Only treatment with hyperimmune plasma resulted in reduced viral load. ? Only treatment with monoclonal antibody m336 resulted in reduced gross pathology. ? No histological differences were observed between untreated and treated common marmosets. 1.?Introduction Middle East respiratory syndrome coronavirus (MERS-CoV) was first detected in Rivanicline oxalate 2012 in a resident of Saudi Arabia, and has since resulted in > 1900 cases with a case fatality rate of TGFA 36% (WHO, 2015). The severity and the epidemic potential of MERS-CoV highlights the importance of the development of treatment options. As of yet, no specific vaccine or antiviral treatment against MERS-CoV is usually available. Few studies have been published investigating the effectiveness of existing antiviral treatments, and no treatments have been thoroughly assessed in clinical trials as of yet. Convalescent plasma has been identified by the World Health Organization (WHO) and the International Severe Acute Respiratory and Emerging Contamination Consortium (ISARIC) as a potential treatment against MERS-CoV to reduce clinical consequences of MERS-CoV contamination (WHO and ISARIC, 2013, WHO, 2014) and recently a study protocol was developed to investigate the feasibility of convalescent plasma treatment in MERS patients (Arabi et?al., 2015). (Jiang et?al., 2014, Tang et?al., 2014, Ying et?al., 2014). Efficacy of mAbs has been assessed in several MERS-CoV mouse models generally showing reduction in virus replication (Corti et?al., 2015, Li et?al., 2015, Pascal et?al., 2015, Luke et?al., 2016). These studies suggest that mAbs have potential as MERS-CoV treatment. The mAb m336, identified from a large phage-displayed antibody library panned against recombinant MERS-CoV spike protein receptor binding domain name, inhibited 90% MERS-CoV pseudovirus contamination at a concentration of 0.039?g/ml (Ying et?al., 2014). m336 was shown to almost completely overlap with the binding site of DPP4 and mimic critical interactions between DPP4 Rivanicline oxalate and the MERS-CoV spike protein (Modjarrad et?al., 2016). It has therefore been speculated that this potential for viral escape mutants might be limited by the requirement of the spike protein to bind to DPP4 (Ying et?al., 2015). Prophylactic treatment with m336 resulted in significantly reduced viral titer in rabbit lung tissue (Houser et?al., 2016) and both prophylactic and therapeutic treatment with m336 guarded mice against lethality by MERS-CoV contamination (Agrawal et?al., 2016). Here we assess the effect of treatment with marmoset-derived hyperimmune plasma as well as the human mAb m336 on disease outcome in the recently developed marmoset MERS-CoV contamination model, which recapitulates severe respiratory disease (Falzarano et?al., 2014). 2.?Materials and methods 2.1. Ethics statement Approval of animal experiments was obtained from the Institutional Animal Care and Use Committee at Rocky Mountain Laboratories. All experiments were performed in an Association for Assessment and Accreditation of Laboratory Animal Care-approved facility by certified staff, following the guidelines and basic principles in the United States Public Health Support Policy on Humane Care and Use of Laboratory Animals, the NIH Rivanicline oxalate Guide for the Care and Use of Laboratory Animals and the Animal Welfare Act, United States Department of Agriculture. The Institutional Biosafety Committee (IBC) approved work with infectious MERS-CoV strains under BSL3 conditions. Sample inactivation was performed according to IBC-approved standard operating procedures for removal of specimens from high containment. 2.2. Generation of MERS-CoV hyperimmune sera Hyperimmune plasma was obtained from a convalescent common marmoset (transcribed UpE MERS-CoV RNA were run on the digital droplet PCR (Biorad) in quadruplicate to determine genome copies. Hereafter, dilutions were run on the Rotor-GeneTM in quadruplicate. The last dilution to give a Ct-value in all replicates was defined as the limit of detection (LOD) in genome copies. Finally, the number of genome copies was decided in the MERS-CoV dilutions with known titer, and LOD was calculated in TCID50 equivalent. 2.10. Infectious virus titration Small tissue samples (up to 100?mg) in 1?ml of 2% DMEM were homogenized. Hereafter, MERS-CoV was titrated in quadruplicate in VeroE6 cells; cells were inoculated with ten-fold serial dilutions of tissue homogenate,.