A human/murine chimeric fab antibody neutralizes anthrax lethal toxin in vitro.

Clinical & Developmental Immunology Pub Date : 2013-01-01 Epub Date: 2013-06-05 DOI:10.1155/2013/475809

Guipeng Ding, Ximin Chen, Jin Zhu, Nicholas S Duesbery, Xunjia Cheng, Brian Cao

{"title":"A human/murine chimeric fab antibody neutralizes anthrax lethal toxin in vitro.","authors":"Guipeng Ding, Ximin Chen, Jin Zhu, Nicholas S Duesbery, Xunjia Cheng, Brian Cao","doi":"10.1155/2013/475809","DOIUrl":null,"url":null,"abstract":"<p><p>Human anthrax infection caused by exposure to Bacillus anthracis cannot always be treated by antibiotics. This is mostly because of the effect of the remaining anthrax toxin in the body. Lethal factor (LF) is a component of lethal toxin (LeTx), which is the major virulence of anthrax toxin. A murine IgG monoclonal antibody (mAb) against LF with blocking activity (coded LF8) was produced in a previous study. In this report, a human/murine chimeric Fab mAb (coded LF8-Fab) was developed from LF8 by inserting murine variable regions into human constant regions using antibody engineering to reduce the incompatibility of the murine antibody for human use. The LF8-Fab expressed in Escherichia coli could specifically identify LF with an affinity of 3.46 × 10(7) L/mol and could neutralize LeTx with an EC50 of 85 μ g/mL. Even after LeTx challenge at various time points, the LF8-Fab demonstrated protection of J774A.1 cells in vitro. The results suggest that the LF8-Fab might be further characterized and potentially be used for clinical applications against anthrax infection. </p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"475809"},"PeriodicalIF":0.0000,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/475809","citationCount":"10","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical & Developmental Immunology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/2013/475809","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2013/6/5 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 10

Abstract

Human anthrax infection caused by exposure to Bacillus anthracis cannot always be treated by antibiotics. This is mostly because of the effect of the remaining anthrax toxin in the body. Lethal factor (LF) is a component of lethal toxin (LeTx), which is the major virulence of anthrax toxin. A murine IgG monoclonal antibody (mAb) against LF with blocking activity (coded LF8) was produced in a previous study. In this report, a human/murine chimeric Fab mAb (coded LF8-Fab) was developed from LF8 by inserting murine variable regions into human constant regions using antibody engineering to reduce the incompatibility of the murine antibody for human use. The LF8-Fab expressed in Escherichia coli could specifically identify LF with an affinity of 3.46 × 10(7) L/mol and could neutralize LeTx with an EC50 of 85 μ g/mL. Even after LeTx challenge at various time points, the LF8-Fab demonstrated protection of J774A.1 cells in vitro. The results suggest that the LF8-Fab might be further characterized and potentially be used for clinical applications against anthrax infection.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

人/鼠嵌合fab抗体在体外中和炭疽致死毒素。

暴露于炭疽芽孢杆菌引起的人类炭疽感染并不总是用抗生素治疗。这主要是由于体内残留的炭疽毒素的影响。致死性因子(LF)是致死性毒素(LeTx)的组成部分，是炭疽毒素的主要毒力。在先前的研究中产生了一种具有阻断活性的抗LF的小鼠IgG单克隆抗体(mAb)(编码LF8)。在本报告中，利用抗体工程技术将LF8的鼠可变区插入人恒定区，以减少鼠抗体对人使用的不相容性，开发了人/鼠嵌合Fab单抗(编码LF8-Fab)。在大肠杆菌中表达的LF8-Fab能特异性识别LF，亲和力为3.46 × 10(7) L/mol，中和LeTx的EC50为85 μ g/mL。即使在不同时间点的LeTx挑战之后，LF8-Fab也展示了对J774A的保护。1细胞体外培养。结果表明，LF8-Fab可能被进一步表征，并有可能用于抗炭疽感染的临床应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊