期刊
HUMAN VACCINES & IMMUNOTHERAPEUTICS
卷 10, 期 10, 页码 2843-2852出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/21645515.2014.971641
关键词
antibody; PcrV; Pseudomonas aeruginosa; type III secretion system; V-antigen; CF; cystic fibrosis; Fab; fragment antigen binding; Fc; fragment crystallizable region; immunoglobulin G; IgG; mAb; monoclonal antibody; MDR; multidrug resistant; MDRP; multidrug resistant Pseudomonas aeruginosa; P; aeruginosa; Pseudomonas aeruginosa; TTSS; type III secretion system; TTS; type III secretory; VAP; ventilator-associated pneumonia
资金
- KAKENHI [24390403]
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Grants-in-Aid for Scientific Research [26670791, 24390403] Funding Source: KAKEN
Pseudomonas aeruginosa is an opportunistic bacterial pathogen that causes fatal acute lung infections in critically ill individuals. Its pathogenesis is associated with bacterial virulence conferred by the type III secretion system (TTSS), through which P. aeruginosa causes necrosis of the lung epithelium and disseminates into the circulation, resulting in bacteremia, sepsis, and mortality. TTSS allows P. aeruginosa to directly translocate cytotoxins into eukaryotic cells, inducing cell death. The P. aeruginosa V-antigen PcrV, a homolog of the Yersinia V-antigen LcrV, is an indispensable contributor to TTS toxin translocation. Vaccination against PcrV ensures the survival of challenged mice and decreases lung inflammation and injury. Both the rabbit polyclonal anti-PcrV antibody and the murine monoclonal anti-PcrV antibody, mAb166, inhibit TTS toxin translocation. mAb166 IgG was cloned, and a molecular engineered humanized anti-PcrV IgG antigen-binding fragment, KB001, was developed for clinical use. KB001 is currently undergoing Phase-II clinical trials for ventilator-associated pneumonia in France and chronic pneumonia in cystic fibrosis in USA. In these studies, KB001 has demonstrated its safety, a favorable pharmacokinetic profile, and promising potential as a nonantibiotic strategy to reduce airway inflammation and damage in P. aeruginosa pneumonia.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据