title: Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus.
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.
authors.affiliation: Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland; Humabs BioMed SA, 6500 Bellinzona, Switzerland;
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
authors.affiliation: 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;
authors.forename: Jincun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland;
authors.forename: Mattia
authors.initials: M
authors.lastname: Pedotti
authors.affiliation: Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland;
authors.forename: Luca
authors.initials: L
authors.lastname: Simonelli
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Agnihothram
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Craig
authors.initials: C
authors.lastname: Fett
authors.affiliation: Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland;
authors.forename: Blanca
authors.initials: B
authors.lastname: Fernandez-Rodriguez
authors.affiliation: Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland;
authors.forename: Mathilde
authors.initials: M
authors.lastname: Foglierini
authors.affiliation: Humabs BioMed SA, 6500 Bellinzona, Switzerland;
authors.forename: Gloria
authors.initials: G
authors.lastname: Agatic
authors.affiliation: Humabs BioMed SA, 6500 Bellinzona, Switzerland;
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Vanzetta
authors.affiliation: Microbiology Services Colindale, Public Health England, London NW9 5HT, United Kingdom;
authors.forename: Robin
authors.initials: R
authors.lastname: Gopal
authors.affiliation: Guy's and St. Thomas' National Health Service Foundation Trust, London SE1 7EH, United Kingdom;
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Langrish
authors.affiliation: 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;
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Barrett
authors.affiliation: Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland;
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.affiliation: 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;
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Baric
authors.affiliation: Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland;
authors.forename: Luca
authors.initials: L
authors.lastname: Varani
authors.affiliation: Microbiology Services Colindale, Public Health England, London NW9 5HT, United Kingdom;
authors.forename: Maria
authors.initials: M
authors.lastname: Zambon
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52240;
authors.forename: Stanley
authors.initials: S
authors.lastname: Perlman
authors.affiliation: 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.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001665:Binding Sites; D016466:CHO Cells; D018352:Coronavirus Infections / Q000276:immunology / Q000821:virology; D006224:Cricetinae; D003412:Cricetulus; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D065207:Middle East Respiratory Syndrome Coronavirus / Q000187:drug effects*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D064370:Spike Glycoprotein, Coronavirus / Q000737:chemistry; D014765:Viral Vaccines
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D064370:Spike Glycoprotein, Coronavirus; D014765:Viral Vaccines; D018819:Dipeptidyl Peptidase 4
keywords: MERS-CoV; emerging viruses; neutralizing antibody; serotherapy