PHASE I, DOSE ESCALATION, SAFETY & ENTEROTOXIGENIC E COLI

第一阶段，剂量递增，安全性

• 批准号: 6264081
• 负责人: DAVID A SACK
• 金额: $ 0.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6264081
• 关键词: Escherichia coli; antibacterial agents; antibody formation; attenuated microorganism; bacterial antigens; bacterial vaccines; clinical research; clinical trial phase I; colony stimulating factor; drug administration rate /duration; enterotoxins; feces analysis; genetic strain; human subject; human therapy evaluation; immunity; immunization; live vaccine; oral administration; vaccine development

Hypothesis: That volunteers who receive the new candidate oral vaccines for enterotoxigenic E. coli, strains PTL002 and PTL003, in doses of 5x10(7), 5x10(9) and 5x10(10) per dose will excrete the vaccine strain in their stool, will have no symptoms related to ingesting the strains, and will develop intestinal antibodies to the E. coli colonization factor antigen, CFA II. These attenuated strains of E. coli produce neither heat labile toxin (LT) nor heat stable toxin (ST) but do express CFA II antigen and they have metabolic defects that limit their growth. It is hoped that when they are given orally, they will stimulate protective anti-CFA immunity.

假设：接受产肠毒素大肠杆菌菌株 PTL002 和 PTL003 的新候选口服疫苗（每剂剂量为 5x10(7)、5x10(9) 和 5x10(10)）的志愿者将在粪便中排出疫苗菌株，不会出现与摄入菌株相关的症状，并且会产生针对大肠杆菌定植因子抗原（CFA II）的肠道抗体。 这些大肠杆菌减毒菌株既不产生热不稳定毒素 (LT) 也不产生热稳定毒素 (ST)，但表达 CFA II 抗原，并且它们具有限制其生长的代谢缺陷。 人们希望当口服它们时，它们会刺激保护性抗 CFA 免疫力。