MILK IMMUNOGLOBULIN FOR FIMBRIAL ADHESION WITH ENTEROTOXIGENIC ECOLI

牛奶免疫球蛋白与产肠毒素大肠杆菌的菌毛粘附

• 批准号: 7604675
• 负责人: ROBIN MCKENZIE
• 金额: $ 1.05万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604675
• 关键词: Adhesions; Age-Years; Antigens; Area; Baltimore; Binding; Bos taurus; Buffers; Cattle; Colostrum; Computer Retrieval of Information on Scientific Projects Database; Consent; Daily; Development; Diarrhea; Distal; Dose; End Point; Enrollment; Eukaryotic Cell; Feces; Fimbria of hippocampus; Funding; Grant; Harvest; Immunization; Immunoglobulin G; Immunoglobulins; Infant formula; Inpatients; Institution; Lactose; Localized; Mediating; Methods; Milk; Minor; Oral; Patient currently pregnant; Pilum; Powder dose form; Preparation; Process; Randomized; Recruitment Activity; Research; Research Personnel; Resources; Sodium Bicarbonate; Source; Treatment Protocols; United States National Institutes of Health; Universities; Upper arm; Virulence; Water; Weight; colonization factor antigens; day; double-blind placebo controlled trial; enterotoxigenic Escherichia coli; feeding; healthy volunteer; prototype; volunteer; ward

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Colonization factor antigen I (CFA/I) fimbriae is a common colonization factor and key virulence determinant of enterotoxigenic Escherichia coli (ETEC). CFA/I fimbriae are heteropolymeric, consisting of major (CfaB) and minor (CfaE) subunits in a ratio of ca. 1000:1. CfaE is localized to the distal fimbrial tip and mediates binding to eukaryotic cells. Objective. To ascertain whether CfaE functions as a protective antigen, we performed a three-armed randomized, double-blinded, placebo-controlled trial in which 31 volunteers received hyperimmune bovine milk immunoglobulin (BIgG) against CfaE (n=10), CFA/I (n=10), or a lactose-free infant formula (LactoFree LIPIL) control preparation (n=11), followed by challenge with the prototype CFA/I-ETEC strain H10407 (LTST; CFA/I; O78:H11). Methods. The two hyperimmune BIgG preparations were generated by serial parenteral immunization of pregnant cows with purified dscCfaE or CFA/I. Early colostrums was harvested and processed to yield a powdered lyophilate enriched for IgG. Healthy volunteers between 18-45 years of age were recruited from the Baltimore area, consented, enrolled, and admitted to the inpatient ward of Johns Hopkins University 3 days before challenge. Starting two days before challenge, volunteers were begun on a thrice daily oral regimen of active BIgG preparation or control, with each unit dose (1 g IgG, total weight, 2.4 - 2.8 g) being mixed in water buffered with sodium bicarbonate (2.8 g per dose) and administered 15 minutes after each meal. Subjects were fed 1 x 1010 cfu ETEC strain H10407 with sodium bicarbonate buffer and followed for five days for development of diarrhea. The primary endpoint of diarrhea was defined as 1 loose stool of ? 300 g within 120 h of challenge or at least 2 loose stools totaling ? 200 g during any 48 h period within 120 h of challenge.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 定植因子抗原 I (CFA/I) 菌毛是产肠毒素大肠杆菌 (ETEC) 的常见定植因子和关键毒力决定因素。 CFA/I 菌毛是杂聚体，由主要 (CfaB) 和次要 (CfaE) 亚基组成，比例为 ca. 1000:1。 CfaE 位于远端菌毛尖端并介导与真核细胞的结合。 客观的。 为了确定 CfaE 是否起到保护性抗原的作用，我们进行了一项三组随机、双盲、安慰剂对照试验，其中 31 名志愿者接受了针对 CfaE (n=10)、CFA/I (n=10) 的超免疫牛乳免疫球蛋白 (BIgG) 或无乳糖婴儿配方奶粉 (LactoFree LIPIL) 对照制剂 (n=11)，然后 通过原型 CFA/I-ETEC 菌株 H10407 (LTST; CFA/I; O78:H11) 的挑战。 方法。 这两种超免疫 BIgG 制剂是通过使用纯化的 dscCfaE 或 CFA/I 对怀孕奶牛进行连续胃肠外免疫而产生的。 早期初乳被收获并加工以产生富含 IgG 的粉末状冻干物。 从巴尔的摩地区招募18-45岁的健康志愿者，在攻击前3天征得同意、登记并入住约翰·霍普金斯大学住院病房。 从攻击前两天开始，志愿者开始每日三次口服活性 BIgG 制剂或对照方案，每个单位剂量（1 g IgG，总重 2.4 - 2.8 g）与碳酸氢钠缓冲的水（每剂 2.8 g）混合，每餐后 15 分钟给药。 受试者喂食 1 x 1010 cfu ETEC 菌株 H10407 和碳酸氢钠缓冲液，并随访五天以观察是否出现腹泻。 腹泻的主要终点定义为 1 次稀便？攻击后 120 小时内摄入 300 克或总共至少 2 次稀便？挑战后 120 小时内的任何 48 小时内 200 g。