MILK IMMUNOGLOBULIN FOR FIMBRIAL ADHESION WITH ENTEROTOXIGENIC ECOLI

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 定殖因子抗原I（CFA/I）菌毛是产肠毒素大肠杆菌（ETEC）常见的定殖因子和关键毒力决定因子。 CFA/I菌毛是杂聚的，由主要亚基（CfaB）和次要亚基（CfaE）组成，比例约为10%。一千比一。 CfaE定位于远端菌毛尖端并介导与真核细胞的结合。 Objective. 为了确定CfaE是否具有保护性抗原的功能，我们进行了一项三臂随机、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）或无乳糖婴儿配方奶粉的超免疫牛乳免疫球蛋白（BIgG）（LactoFree LIPIL）对照制剂（n=11），然后用原型CFA/I-ETEC菌株H10407（LTST; CFA/I; O 78：H11）攻毒。 方法. 通过用纯化的dscCfaE或CFA/I对妊娠母牛进行系列胃肠外免疫来产生两种超免疫BIgG制剂。 收获早期初乳并加工以产生富含IgG的粉末状冻干物。 从巴尔的摩地区招募18-45岁之间的健康志愿者，同意，登记，并在攻击前3天入住约翰霍普金斯大学的住院病房。 从攻击前两天开始，志愿者开始每天三次口服活性BIgG制剂或对照方案，将每个单位剂量（1g IgG，总重量，2.4 - 2.8g）混合在用碳酸氢钠缓冲的水中（每剂量2.8g），并在每餐后15分钟给药。 给受试者喂食含1 x 1010 cfu ETEC菌株H10407的碳酸氢钠缓冲液，并随访5天以观察腹泻的发生。 腹泻的主要终点定义为1次稀便？攻毒后120小时内300 g或总计至少2次稀便？在攻毒后120小时内的任何48小时内，200 g。

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.