Potent neutralization of anthrax edema toxin by a humanized monoclonal antibody that competes with calmodulin for edema factor binding

被引：45

作者：

Chen, Zhaochun ^{[1
]}

Moayeri, Mahtab ^{[2
]}

Zhao, Huaying ^{[3
]}

Crown, Devorah ^{[2
]}

Leppla, Stephen H. ^{[2
]}

Purcell, Robert H. ^{[1
]}

机构：

[1] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA

[2] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA

[3] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 32期

基金：

美国国家卫生研究院;

关键词：

PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; LETHAL FACTOR; ADENYLYL-CYCLASE; INHALATIONAL ANTHRAX; GENETIC IMMUNIZATION; KINASE-KINASE; IN-VIVO; IMMUNITY; PROTEIN;

D O I：

10.1073/pnas.0906581106

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：

This study describes the isolation and characterization of a neutralizing monoclonal antibody (mAb) against anthrax edema factor, EF13D. EF13D neutralized edema toxin (ET)-mediated cyclic AMP (cAMP) responses in cells and protected mice from both ET-induced footpad edema and systemic ET-mediated lethality. The antibody epitope was mapped to domain IV of EF. The mAb was able to compete with calmodulin (CaM) for EF binding and displaced CaM from EF-CaM complexes. EF-mAb binding affinity (0.05-0.12 nM) was 50- to 130-fold higher than that reported for EF-CaM. This anti-EF neutralizing mAb could potentially be used alone or with an anti-PA mAb in the emergency prophylaxis and treatment of anthrax infection.

引用

收藏

页码：13487 / 13492

页数：6

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