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：志愿者接受了新的肠出血性大肠杆菌候选口服疫苗。大肠杆菌菌株PTL002和PTL003，以每剂5 × 10（7）、5 × 10（9）和5 × 10（10）的剂量接种后，将在粪便中排泄疫苗菌株，不会出现与摄入菌株相关的症状，并会产生针对大肠杆菌的肠道抗体。大肠杆菌定植因子抗原 这些E.大肠杆菌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，当它们口服时，它们将刺激保护性的抗CFA免疫力。