tetano
Editor, Senior Moderator
[h=1]Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus[/h]
[h=2]Significance[/h] Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe respiratory disease with a high mortality rate. There is no licensed vaccine or antiviral for MERS. Here we isolated for the first time, to our knowledge, a potent MERS-CoV?neutralizing antibody from memory B cells of an infected individual. This antibody binds to a novel site on the viral Spike protein, neutralizes by interfering with the binding to the cellular receptor CD26, and is highly effective both in prophylaxis and in therapy in a relevant mouse model. This antibody can be developed for prophylaxis, for postexposure prophylaxis, or for the treatment of severe MERS-CoV infections.
[h=2]Abstract[/h] 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.
full article
http://www.pnas.org/content/112/33/10473
- Davide Corti [SUP]a[/SUP] , [SUP]b[/SUP] , [SUP]1[/SUP] ,
- Jincun Zhao [SUP]c[/SUP] , [SUP]d[/SUP] , [SUP]1[/SUP] ,
- Mattia Pedotti [SUP]a[/SUP] ,
- Luca Simonelli [SUP]a[/SUP] ,
- Sudhakar Agnihothram [SUP]e[/SUP] ,
- Craig Fett [SUP]e[/SUP] ,
- Blanca Fernandez-Rodriguez [SUP]a[/SUP] ,
- Mathilde Foglierini [SUP]a[/SUP] ,
- Gloria Agatic [SUP]b[/SUP] ,
- Fabrizia Vanzetta [SUP]b[/SUP] ,
- Robin Gopal [SUP]f[/SUP] ,
- Christopher J. Langrish [SUP]g[/SUP] ,
- Nicholas A Barrett [SUP]g[/SUP] , [SUP]h[/SUP] ,
- Federica Sallusto [SUP]a[/SUP] ,
- Ralph S. Baric [SUP]e[/SUP] , [SUP]i[/SUP] ,
- Luca Varani [SUP]a[/SUP] ,
- Maria Zambon [SUP]f[/SUP] ,
- Stanley Perlman [SUP]c[/SUP] , and
- Antonio Lanzavecchia [SUP]a[/SUP] , [SUP]j[/SUP] , [SUP]2[/SUP]
- [SUP]a[/SUP]Immune Regulation Unit, Institute for Research in Biomedicine, Universit? della Svizzera Italiana, 6500 Bellinzona, Switzerland;
- [SUP]b[/SUP] Humabs BioMed SA, 6500 Bellinzona, Switzerland;
- [SUP]c[/SUP]Department of Microbiology, University of Iowa, Iowa City, IA 52240;
- [SUP]d[/SUP]State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China;
- [SUP]e[/SUP]Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
- [SUP]f[/SUP]Microbiology Services Colindale, Public Health England, London NW9 5HT, United Kingdom;
- [SUP]g[/SUP] Guy?s and St. Thomas? National Health Service Foundation Trust, London SE1 7EH, United Kingdom;
- [SUP]h[/SUP] King?s College London, Strand, London WC2R 2LS, United Kingdom;
- [SUP]i[/SUP]Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
- [SUP]j[/SUP]Institute of Microbiology, Eidgen?ssische Technische Hochschule Zurich, 8093 Zurich, Switzerland
- Edited by Michael B. A. Oldstone, The Scripps Research Institute, La Jolla, CA, and approved June 29, 2015 (received for review May 25, 2015)
[h=2]Significance[/h] Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe respiratory disease with a high mortality rate. There is no licensed vaccine or antiviral for MERS. Here we isolated for the first time, to our knowledge, a potent MERS-CoV?neutralizing antibody from memory B cells of an infected individual. This antibody binds to a novel site on the viral Spike protein, neutralizes by interfering with the binding to the cellular receptor CD26, and is highly effective both in prophylaxis and in therapy in a relevant mouse model. This antibody can be developed for prophylaxis, for postexposure prophylaxis, or for the treatment of severe MERS-CoV infections.
[h=2]Abstract[/h] 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.
full article
http://www.pnas.org/content/112/33/10473