DEVELOPMENT OF AN ANTIDOTE FOR E COLI 0157--H7 VEROTOXIN

E.大肠杆菌O 157：H7是一种新出现的食源性致病菌， 发病率和死亡率。估计有20，000例E。 大肠杆菌0157：H7感染在美国每年。但只有 11个州要求向州卫生局报告病例 因此，案件的实际数量可能要多得多。 高22%的儿童获得E。大肠杆菌O 157：H7 感染会产生潜在致命并发症，例如 溶血性尿毒综合征（HUS）。出现并发症的患者 必须长期住院，而且往往需要终生 肾透析或肾移植。HUS被认为是由 由致病细菌产生的verotoxins，并且没有 抗毒素可供临床使用。Ophidian Pharmaceuticals 本文提出开发E.大肠杆菌0157：H7抗verotoxin 大规模生产治疗药物的专有方法 来自超免疫母鸡的鸡蛋的多克隆抗体。高纯度 禽抗毒素已被证明具有上级毒素- 当用于胃肠外或肠内时的中和效力 给药方案。用纯E.杆菌o 157：H7 维罗毒素，然后制备蛋黄免疫球蛋白 分数所得抗体将在体外进行表征 通过免疫化学分析和vero中的毒素中和 细胞分析抗维罗毒素的治疗效果将是 在小鼠HUS模型中使用肠内或肠外途径进行体内评估。 肠胃外抗维罗毒素给药。这些研究将（i） 提供了治疗效用的实验证据 E.大肠杆菌O 157：H7疾病，如HUS， 和ii）确定是否可以通过以下方法阻止疾病进展： 肠内施用的抗维罗毒素和/或抗维罗毒素是否 在肠胃外给药时有效。

E. coli Ol57:H7 is an emerging food-borne pathogen with substantial morbidity and mortality. There are an estimated 20,000 cases of E. coli 0157:H7 infection per year in the United States. However, only 11 states require reporting of the cases to the State Health Department; hence, the actual number of cases is likely to be much higher. Twenty-two percent of children acquiring E. coli Ol57:H7 infection develop potentially fatal complications, such as hemolytic uremic syndrome (HUS). Patients who develop complications must be hospitalized for long periods, and often require life-long kidney dialysis or kidney transplants. HUS is believed to be caused by verotoxins produced by the offending bacterium, and there are no antitoxins available for clinical use. Ophidian Pharmaceuticals herein proposes to develop E. coli Ol57:H7 antiverotoxin using proprietary methods for the large-scale production of therapeutic polyclonal antibodies from eggs of hyperimmune hens. High-purity avian antitoxins have been shown to have superior toxin- neutralizing potency when used in either a parenteral or enteral dosing regimen. Hens will be immunized with pure E. coli O157:H7 verotoxins, followed by preparation of yolk immunoglobulin fractions. The resulting antibodies will be characterized in vitro by immunochemical analysis and by toxin neutralization in a vero cell assay. The therapeutic efficacy of antiverotoxin will be assessed in vivo in a mouse HUS model using either enteral or parenteral antiverotoxin administration. These studies will i) provide experimental evidence for the therapeutic utility of antiverotoxin antibodies in E. coli O157:H7 disease, such as HUS, and ii) determine if disease progression can be arrested by antiverotoxin enterally administered and/or whether antiverotoxin is effective when given parenterally.