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

Davide Corti, Jincun Zhao, Mattia Pedotti, Luca Simonelli, Sudhakar Agnihothram, Craig Fett, Blanca Fernandez-Rodriguez, Mathilde Foglierini, Gloria Agatic, Fabrizia Vanzetta, Robin Gopal, Christopher J. Langrish, Nicholas A. Barrett, Federica Sallusto, Ralph S. Baric, Luca Varani, Maria Zambon, Stanley Perlman, Antonio Lanzavecchia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

166 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)10473-10478
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number33
DOIs
Publication statusPublished - 18 Aug 2015

Bibliographical note

Publisher Copyright:
© 2015, National Academy of Sciences. All rights reserved.

Keywords

  • Emerging viruses
  • MERS-CoV
  • Neutralizing antibody
  • Serotherapy

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