A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In Vitro
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...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2013/475809 |
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| author | Guipeng Ding Ximin Chen Jin Zhu Nicholas S. Duesbery Xunjia Cheng Brian Cao |
| author_facet | Guipeng Ding Ximin Chen Jin Zhu Nicholas S. Duesbery Xunjia Cheng Brian Cao |
| author_sort | Guipeng Ding |
| collection | DOAJ |
| description | 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 3.46×107 L/mol and could neutralize LeTx with an EC50 of 85 μg/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. |
| format | Article |
| id | doaj-art-b96149038bc4469192432aa106766fdb |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
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| series | Clinical and Developmental Immunology |
| spelling | doaj-art-b96149038bc4469192432aa106766fdb2025-02-03T06:13:07ZengWileyClinical and Developmental Immunology1740-25221740-25302013-01-01201310.1155/2013/475809475809A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In VitroGuipeng Ding0Ximin Chen1Jin Zhu2Nicholas S. Duesbery3Xunjia Cheng4Brian Cao5Department of Pathology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, ChinaDepartment of Pathology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, ChinaHuadong Medical Institute of Biotechniques, 293 East Zhongshan Road, Nanjing 210002, ChinaLaboratory of Cancer and Developmental Cell Biology, Van Andel Research Institute, 333 Bostwick Avenue, Grand Rapids, MI 49503, USADepartment of Medical Microbiology and Parasitology, Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Shanghai 200032, ChinaLaboratory of Antibody Technology, Van Andel Research Institute, 333 Bostwick Avenue, Grand Rapids, MI 49503, USAHuman 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 3.46×107 L/mol and could neutralize LeTx with an EC50 of 85 μg/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.http://dx.doi.org/10.1155/2013/475809 |
| spellingShingle | Guipeng Ding Ximin Chen Jin Zhu Nicholas S. Duesbery Xunjia Cheng Brian Cao A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In Vitro Clinical and Developmental Immunology |
| title | A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In Vitro |
| title_full | A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In Vitro |
| title_fullStr | A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In Vitro |
| title_full_unstemmed | A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In Vitro |
| title_short | A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In Vitro |
| title_sort | human murine chimeric fab antibody neutralizes anthrax lethal toxin in vitro |
| url | http://dx.doi.org/10.1155/2013/475809 |
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