An Engineered Human Antibody Fab Fragment Specific for Pseudomonas aeruginosa PcrV Antigen Has Potent Antibacterial Activity
An Engineered Human Antibody Fab Fragment Specific for Pseudomonas aeruginosa PcrV Antigen Has Potent Antibacterial Activity
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DOI：
10.1128/iai.00815-08
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发表时间：
2009-03-01
影响因子：
3.1
通讯作者：
Bebbington, Christopher
中科院分区：
文献类型：
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作者：
Baer, Mark;Sawa, Teiji;Bebbington, Christopher
铜绿假单胞菌是一种条件致病菌，可通过III型分泌系统（TTSS）释放外毒素引起急性肺损伤和死亡。PcrV是TTSS的重要结构蛋白。已经鉴定了以高亲和力结合铜绿假单胞菌PcrV蛋白的工程化人抗体Fab片段，并且其具有针对TTSS的有效体外中和活性。将单剂量的Fab滴注到小鼠的肺中提供了针对铜绿假单胞菌的致死性肺攻击的保护，并导致肺中活细菌计数的显著减少。这些结果表明，通过缺乏抗体Fc介导的效应子功能的Fab阻断TTSS可足以有效清除肺部铜绿假单胞菌感染。
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.