MILK IMMUNOGLOBULIN FOR FIMBRIAL ADHESION WITH ENTEROTOXIGENIC ECOLI

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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.