Journal article
Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus
Proceedings of the National Academy of Sciences of the United States of America, Vol.112(33), pp.10473-10478
08/18/2015
DOI: 10.1073/pnas.1510199112
PMCID: PMC4547275
PMID: 26216974
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.
Details
- Title: Subtitle
- Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus
- Creators
- Davide Corti - Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland; Humabs BioMed SA, 6500 Bellinzona, SwitzerlandJincun Zhao - Department of Microbiology, University of Iowa, Iowa City, IA 52240; State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, ChinaMattia Pedotti - Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, SwitzerlandLuca Simonelli - Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, SwitzerlandSudhakar Agnihothram - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599Craig Fett - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599Blanca Fernandez-Rodriguez - Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, SwitzerlandMathilde Foglierini - Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, SwitzerlandGloria Agatic - Humabs BioMed SA, 6500 Bellinzona, SwitzerlandFabrizia Vanzetta - Humabs BioMed SA, 6500 Bellinzona, SwitzerlandRobin Gopal - Microbiology Services Colindale, Public Health England, London NW9 5HT, United KingdomChristopher J Langrish - Guy's and St. Thomas' National Health Service Foundation Trust, London SE1 7EH, United KingdomNicholas A Barrett - Guy's and St. Thomas' National Health Service Foundation Trust, London SE1 7EH, United Kingdom; King's College London, Strand, London WC2R 2LS, United KingdomFederica Sallusto - Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, SwitzerlandRalph S Baric - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599Luca Varani - Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, SwitzerlandMaria Zambon - Microbiology Services Colindale, Public Health England, London NW9 5HT, United KingdomStanley Perlman - Department of Microbiology, University of Iowa, Iowa City, IA 52240Antonio Lanzavecchia - Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland; Institute of Microbiology, Eidgenössische Technische Hochschule Zurich, 8093 Zurich, Switzerland lanzavecchia@irb.usi.ch
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences of the United States of America, Vol.112(33), pp.10473-10478
- DOI
- 10.1073/pnas.1510199112
- PMID
- 26216974
- PMCID
- PMC4547275
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- United States
- Grant note
- R01 AI110700 / NIAID NIH HHS HHSN272201000013I / PHS HHS AI085524 / NIAID NIH HHS AI110700 / NIAID NIH HHS R01 AI091322 / NIAID NIH HHS P01 AI060699 / NIAID NIH HHS R01 AI085524 / NIAID NIH HHS HHSN272201000013C / NIAID NIH HHS
- Language
- English
- Date published
- 08/18/2015
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9983777348002771
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