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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Potent neutralization of anthrax edema toxin by a humanized monoclonal antibody that competes with calmodulin for edema factor binding
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Potent neutralization of anthrax edema toxin by a humanized monoclonal antibody that competes with calmodulin for edema factor binding

机译:与钙调蛋白竞争水肿因子结合的人源化单克隆抗体可有效中和炭疽水肿毒素

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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.
机译:这项研究描述了针对炭疽浮肿因子EF13D的中和单克隆抗体(mAb)的分离和表征。 EF13D中和了细胞中水肿毒素(ET)介导的循环AMP(cAMP)反应,并保护了小鼠免受ET诱导的足垫水肿和全身性ET介导的致死性。抗体表位定位于EF的IV结构域。 mAb能够与钙调蛋白(CaM)竞争EF结合,并从EF-CaM复合物中置换出CaM。 EF-mAb结合亲和力(0.05-0.12 nM)比EF-CaM的亲和力高50-130倍。该抗EF中和mAb可以单独或与抗PA mAb一起用于紧急预防和治疗炭疽感染。

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    Laboratory of Infectious Diseases, and Bioengineering, National Institutes of Health, Bethesda, MD 20892;

    Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, and Bioengineering, National Institutes of Health, Bethesda, MD 20892;

    National Institute for Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892;

    Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, and Bioengineering, National Institutes of Health, Bethesda, MD 20892;

    Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, and Bioengineering, National Institutes of Health, Bethesda, MD 20892;

    Laboratory of Infectious Diseases, and Bioengineering, National Institutes of Health, Bethesda, MD 20892;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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