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

被引:183
作者
Corti, Davide [1 ,2 ]
Zhao, Jincun [3 ,4 ]
Pedotti, Mattia [1 ]
Simonelli, Luca [1 ]
Agnihothram, Sudhakar [5 ]
Fett, Craig [5 ]
Fernandez-Rodriguez, Blanca [1 ]
Foglierini, Mathilde [1 ]
Agatic, Gloria [2 ]
Vanzetta, Fabrizia [2 ]
Gopal, Robin [6 ]
Langrish, Christopher J. [7 ]
Barrettg, Nicholas A. [7 ,8 ]
Sallusto, Federica [1 ]
Baric, Ralph S. [5 ,9 ]
Varani, Luca [1 ]
Zambon, Maria [6 ]
Perlman, Stanley [3 ]
Lanzavecchia, Antonio [1 ,10 ]
机构
[1] Univ Svizzera Italiana, Inst Res Biomed, Immune Regulat Unit, CH-6500 Bellinzona, Switzerland
[2] Humabs BioMed SA, CH-6500 Bellinzona, Switzerland
[3] Univ Iowa, Dept Microbiol, Iowa City, IA 52240 USA
[4] Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou Inst Resp Dis, State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China
[5] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
[6] Publ Hlth England, Microbiol Serv Colindale, London NW9 5HT, England
[7] Guys & St Thomas Natl Hlth Serv Fdn Trust, London SE1 7EH, England
[8] Kings Coll London, London WC2R 2LS, England
[9] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA
[10] ETH, Inst Microbiol, CH-8093 Zurich, Switzerland
基金
芬兰科学院; 瑞士国家科学基金会;
关键词
MERS-CoV; neutralizing antibody; serotherapy; emerging viruses; RESPIRATORY SYNDROME CORONAVIRUS; MIDDLE-EAST; CONVALESCENT PLASMA; NEUTRALIZING ANTIBODIES; B-CELLS; RECEPTOR; PROTEIN; COV; GENERATION; PNEUMONIA;
D O I
10.1073/pnas.1510199112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 newprophylactic 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.
引用
收藏
页码:10473 / 10478
页数:6
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