通过使用缺乏Fc区域的高亲和力抗毒素抗体片段对炭疽进行被动保护。
Passive protection against anthrax by using a high-affinity antitoxin antibody fragment lacking an Fc region.
作者信息
Mabry Robert, Rani Mridula, Geiger Robert, Hubbard Gene B, Carrion Ricardo, Brasky Kathleen, Patterson Jean L, Georgiou George, Iverson B L
机构信息
Department of Chemical Engineering and Biomedical Engineering, University of Texas at Austin, 1 University Station, Austin, TX 78712, USA.
出版信息
Infect Immun. 2005 Dec;73(12):8362-8. doi: 10.1128/IAI.73.12.8362-8368.2005.
Abstract
Passive immunization has been successfully employed for protection against bacterial and viral infections for over 100 years. Immunoglobulin Fc regions play a critical role in the clearance of bacterial pathogens by mediating antibody-dependent and complement-dependent cytotoxicity. Here we show that antibody fragments engineered to recognize the protective antigen component of the B. anthracis exotoxin with high affinity and conjugated to polyethylene glycol (PEG) for prolonged circulation half-life confer significant protection against inhalation anthrax despite their lack of Fc regions. The speed and lower manufacturing cost of bacterially expressed PEGylated antibody fragments could provide decisive advantages for anthrax prophylaxis. Importantly, our results suggest that PEGylated antibody fragments may represent a unique approach for mounting a rapid therapeutic response to emerging pathogen infections.
摘要
被动免疫已成功应用于预防细菌和病毒感染达100多年。免疫球蛋白Fc区域通过介导抗体依赖性和补体依赖性细胞毒性在清除细菌病原体中发挥关键作用。在此我们表明，经工程改造以高亲和力识别炭疽芽孢杆菌外毒素保护性抗原成分并与聚乙二醇（PEG）偶联以延长循环半衰期的抗体片段，尽管缺乏Fc区域，但仍能对吸入性炭疽提供显著保护。细菌表达的聚乙二醇化抗体片段的速度和较低的制造成本可为炭疽预防提供决定性优势。重要的是，我们的结果表明聚乙二醇化抗体片段可能代表了一种针对新出现的病原体感染迅速做出治疗反应的独特方法。
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