| Literature DB >> 26216974 |
Davide Corti1, Jincun Zhao2, Mattia Pedotti3, Luca Simonelli3, Sudhakar Agnihothram4, Craig Fett4, Blanca Fernandez-Rodriguez3, Mathilde Foglierini3, Gloria Agatic5, Fabrizia Vanzetta5, Robin Gopal6, Christopher J Langrish7, Nicholas A Barrett8, Federica Sallusto3, Ralph S Baric9, Luca Varani3, Maria Zambon6, Stanley Perlman10, Antonio Lanzavecchia11.
Abstract
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.Entities:
Keywords: MERS-CoV; emerging viruses; neutralizing antibody; serotherapy
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Year: 2015 PMID: 26216974 PMCID: PMC4547275 DOI: 10.1073/pnas.1510199112
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN: 0027-8424 Impact factor: 11.205