一种针对铜绿假单胞菌PcrV抗原的工程化人源抗体Fab片段具有强大的抗菌活性。
An engineered human antibody fab fragment specific for Pseudomonas aeruginosa PcrV antigen has potent antibacterial activity.
作者信息
Baer Mark, Sawa Teiji, Flynn Peter, Luehrsen Kenneth, Martinez David, Wiener-Kronish Jeanine P, Yarranton Geoffrey, Bebbington Christopher
机构信息
Kalobios Pharmaceuticals, Inc, South San Francisco, California 94080, USA.
出版信息
Infect Immun. 2009 Mar;77(3):1083-90. doi: 10.1128/IAI.00815-08. Epub 2008 Dec 22.
Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that can cause acute lung injury and mortality through the delivery of exotoxins by the type III secretion system (TTSS). PcrV is an important structural protein of the TTSS. An engineered human antibody Fab fragment that binds to the P. aeruginosa PcrV protein with high affinity has been identified and has potent in vitro neutralization activity against the TTSS. The instillation of a single dose of Fab into the lungs of mice provided protection against lethal pulmonary challenge of P. aeruginosa and led to a substantial reduction of viable bacterial counts in the lungs. These results demonstrate that blocking of the TTSS by a Fab lacking antibody Fc-mediated effector functions can be sufficient for the effective clearance of pulmonary P. aeruginosa infection.
摘要
铜绿假单胞菌是一种机会致病菌，可通过III型分泌系统（TTSS）分泌外毒素，导致急性肺损伤和死亡。PcrV是TTSS的一种重要结构蛋白。已鉴定出一种工程化的人源抗体Fab片段，它能高亲和力地结合铜绿假单胞菌PcrV蛋白，并对TTSS具有强大的体外中和活性。向小鼠肺部单次注入Fab可保护其免受铜绿假单胞菌致死性肺部攻击，并导致肺部活菌数大幅减少。这些结果表明，缺乏抗体Fc介导效应功能的Fab阻断TTSS足以有效清除肺部铜绿假单胞菌感染。
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2
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Chem Biol. 2007 Oct;14(10):1119-27. doi: 10.1016/j.chembiol.2007.08.013.
3
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Anal Biochem. 2006 Dec 1;359(1):112-9. doi: 10.1016/j.ab.2006.08.032. Epub 2006 Sep 22.
4
Bacteremias in patients with severe burn trauma.
Medicina (Kaunas). 2006;42(7):576-9.
5
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Infect Immun. 2006 May;74(5):2742-50. doi: 10.1128/IAI.74.5.2742-2750.2006.
6
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Med Mal Infect. 2006 Feb;36(2):78-91. doi: 10.1016/j.medmal.2005.10.007. Epub 2006 Jan 19.
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Infect Immun. 2005 Dec;73(12):8362-8. doi: 10.1128/IAI.73.12.8362-8368.2005.
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