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Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10473-8. doi: 10.1073/pnas.1510199112. Epub 2015 Jul 27.

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

Author information

1
Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland; Humabs BioMed SA, 6500 Bellinzona, Switzerland;
2
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, China;
3
Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland;
4
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
5
Humabs BioMed SA, 6500 Bellinzona, Switzerland;
6
Microbiology Services Colindale, Public Health England, London NW9 5HT, United Kingdom;
7
Guy's and St. Thomas' National Health Service Foundation Trust, London SE1 7EH, United Kingdom;
8
Guy's and St. Thomas' National Health Service Foundation Trust, London SE1 7EH, United Kingdom; King's College London, Strand, London WC2R 2LS, United Kingdom;
9
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 27599;
10
Department of Microbiology, University of Iowa, Iowa City, IA 52240;
11
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.

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.

KEYWORDS:

MERS-CoV; emerging viruses; neutralizing antibody; serotherapy

Comment in

PMID:
26216974
PMCID:
PMC4547275
DOI:
10.1073/pnas.1510199112
[Indexed for MEDLINE]
Free PMC Article

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