Thanks to Greg Folkers for sending the link to this report in the Journal of Virology: Exceptionally potent neutralization of MERS-CoV by human monoclonal antibodies. The abstract and commentary:
The recently discovered Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to infect humans with high mortality. Specific, highly effective therapeutics and vaccines against the MERS-CoV are urgently needed to save human lives and address the pandemic concerns.
We identified three human monoclonal antibodies (mAbs), m336, m337 and m338, targeting the receptor (CD26/DPP4) binding domain (RBD) of the MERS-CoV spike glycoprotein from a very large naive antibody library (size ∼ 1011). They bound with high affinity — equilibrium dissociation constants equal to 4.2, 9.3 and 15 nM, respectively, as measured by Biacore for Fabs binding to RBD.
The avidity for IgG1 m336, m337 and m338 was even higher — 99, 820 and 560 pM, respectively. The antibodies bound to overlapping epitopes which overlap with the receptor binding site on the RBD as suggested by competition experiments and further supported by site-directed mutagenesis of the RBD and a docking model of the m336-RBD complex. The highest affinity mAb, m336, neutralized both pseudotyped and live MERS-CoV with exceptional potency: 50% neutralization at 0.005 and 0.07 μg/ml, respectively, likely by competing with DPP4 for binding to the S glycoprotein.
The exceptionally high neutralization activity of these antibodies and especially m336 suggests that they have great potential for prophylaxis and therapy of MERS-CoV infection in humans and as a tool for development of vaccine immunogens. The rapid (several weeks) identification of potent mAbs suggests a possibility to use the new large antibody library and related methodology for quick response to public threat resulting from emerging coronaviruses.
IMPORTANCE A novel human coronavirus, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was found to infect humans with a high mortality rate in 2012, just a decade after the appearance of the first highly pathogenic coronavirus, SARS-CoV. There are no effective therapeutics available.
It is highly desirable to find an approach for rapidly developing potent therapeutics against MERS-CoV, which can not only be implemented for MERS treatment, but can also help to develop a platform strategy to combat future emerging coronaviruses.
We report here the identification of human monoclonal antibodies (mAbs) from a large non-immunized antibody library that target the MERS-CoV. One of the antibodies, m336, neutralized the virus with exceptional potency. It therefore may have great potential as a candidate therapeutic and as a reagent to facilitate the development of vaccines against MERS-CoV.