3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology in rhesus monkeys following intratracheal inoculation of MERS-CoV Jordan-n3/2012

Abstract

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1,600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5×106 PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a human anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11-N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment.

Prophylactic efficacy of a human monoclonal antibody against MERS-CoV in the common marmoset

“…Taken together, the prophylactic treatment with LCA60 resulted in a moderate clinical benefit, including reduced respiratory involvement and fewer pathological changes in the lungs of LCA60-treated marmosets. These results are in line with a study in common marmosets where treatment with monoclonal antibodies REGN3048 and REGN3051 resulted in less severe respiratory disease (de Wit et al, 2018), and a study in rhesus macaques where prophylactic treatment with the MERS-CoV neutralizing mAb 3B11eN resulted in a reduced pathologic lung volume using computed tomography (Johnson et al, 2016). Of note, LCA60 was shown to bind to an epitope overlapping with that of 3B11eN and to be 10-fold more potent in terms of viral neutralization (Corti et al, 2015).…”

Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets

“…However, despite promising results in mouse models, the high case-fatality rate in humans, low neutralizing antibody titers in survivors and the inability of many survivors to function as plasma donors due to underlying health issues are considerable hurdles in the implementation of convalescent plasma therapy for MERS patients (Arabi et al, 2016). Monoclonal antibody (mAb) treatment could provide an alternative for convalescent plasma, and several neutralizing monoclonal antibodies have been developed and tested in animal models (Agrawal et al, 2016; https://doi.org/10.1016/j.antiviral.2018.06.006 Received 2 April 2018; Received in revised form 4 June 2018; Accepted 5 June 2018 Corti et al, 2015;Houser et al, 2016;Johnson et al, 2016;Li et al, 2015;Pascal et al, 2015;Qiu et al, 2016).…”

Epidemic and Emerging Coronaviruses (Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome)

“…Various monoclonal and polyclonal antibody preparations with neutralizing activity inhibiting MERS-CoV are now in preclinical models. [136][137][138][139][140] There are no published human data, however, to date on the use of these preparations or of convalescent plasma for treatment of patients with MERS-CoV infection.…”