TY - JOUR
T1 - Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus
AU - Corti, Davide
AU - Zhao, Jincun
AU - Pedotti, Mattia
AU - Simonelli, Luca
AU - Agnihothram, Sudhakar
AU - Fett, Craig
AU - Fernandez-Rodriguez, Blanca
AU - Foglierini, Mathilde
AU - Agatic, Gloria
AU - Vanzetta, Fabrizia
AU - Gopal, Robin
AU - Langrish, Christopher J.
AU - Barrett, Nicholas A.
AU - Sallusto, Federica
AU - Baric, Ralph S.
AU - Varani, Luca
AU - Zambon, Maria
AU - Perlman, Stanley
AU - Lanzavecchia, Antonio
N1 - Publisher Copyright:
© 2015, National Academy of Sciences. All rights reserved.
PY - 2015/8/18
Y1 - 2015/8/18
N2 - 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.
AB - 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.
KW - Emerging viruses
KW - MERS-CoV
KW - Neutralizing antibody
KW - Serotherapy
UR - http://www.scopus.com/inward/record.url?scp=84939863145&partnerID=8YFLogxK
U2 - 10.1073/pnas.1510199112
DO - 10.1073/pnas.1510199112
M3 - Article
C2 - 26216974
AN - SCOPUS:84939863145
SN - 0027-8424
VL - 112
SP - 10473
EP - 10478
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 33
ER -