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Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus

Davide Cortia,b,1, Jincun Zhaoc,d,1, Mattia Pedottia, Luca Simonellia, Sudhakar Agnihothrame, Craig Fette, Blanca Fernandez-Rodrigueza, Mathilde Foglierinia, Gloria Agaticb, Fabrizia Vanzettab, Robin Gopalf, Christopher J. Langrishg, Nicholas A Barrettg,h, Federica Sallustoa, Ralph S. Barice,i, Luca Varania, Maria Zambonf, Stanley Perlmanc, and Antonio Lanzavecchiaa,j,2

Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a previously unidentified coronavirus (CoV), likely transmitted to humans by infected camels. There is no licensed vaccine or antiviral for MERS, therefore new prophylactic and therapeutic strategies to combat human infections are needed. In this study, we describe, for the first time, to our knowledge, the isolation of a potent MERS-CoV–neutralizing antibody from memory B cells of an infected individual. The antibody, named LCA60, binds to a novel site on the spike protein and potently neutralizes infection of multiple MERS-CoV isolates by interfering with the binding to the cellular receptor CD26. Importantly, using mice transduced with adenovirus expressing human CD26 and infected with MERS-CoV, we show that LCA60 can effectively protect in both prophylactic and postexposure settings. This antibody can be used for prophylaxis, for postexposure prophylaxis of individuals at risk, or for the treatment of human cases of MERS-CoV infection. The fact that it took only 4 mo from the initial screening of B cells derived from a convalescent patient for the development of a stable chinese hamster ovary (CHO) cell line producing neutralizing antibodies at more than 5 g/L provides an example of a rapid pathway toward the generation of effective antiviral therapies against emerging viruses.

http://www.pnas.org/content/early/2015/07/21/1510199112