Enterotoxigenic (ETEC) is a leading diarrheagenic bacterial pathogen among travelers and children in resource-limited regions. Adherence to host intestinal cells mediated by ETEC fimbriae is believed as a critical first step in ETEC pathogenesis. These fimbriae are categorized into related classes based on sequence similarity, with members of class 5 ETEC fimbrial family being the best characterized. The eight related members of the class 5 fimbrial family are subdivided into three subclasses (5a, 5b, 5c), which share similar structural arrangements, including a fimbrial tip adhesin. However, sequence variability among the class 5 adhesins may hinder generation of cross-protective antibodies. To better underst... More
Enterotoxigenic (ETEC) is a leading diarrheagenic bacterial pathogen among travelers and children in resource-limited regions. Adherence to host intestinal cells mediated by ETEC fimbriae is believed as a critical first step in ETEC pathogenesis. These fimbriae are categorized into related classes based on sequence similarity, with members of class 5 ETEC fimbrial family being the best characterized. The eight related members of the class 5 fimbrial family are subdivided into three subclasses (5a, 5b, 5c), which share similar structural arrangements, including a fimbrial tip adhesin. However, sequence variability among the class 5 adhesins may hinder generation of cross-protective antibodies. To better understand functional epitopes of the class 5 adhesins and their ability to induce intra-class antibody responses, we produced 28 anti-adhesin monoclonal antibodies (mAbs) to representative adhesins, CfaE, CsbD, CotD, respectively. We determined mAb cross-reactivity, localized the epitopes, and measured functional activity as potency in inhibition of hemagglutination induced by the class 5 ETEC. The mAbs reactivity to a panel of class 5 adhesins in ELISA revealed several reactivity patterns: individual adhesin specificity, intra-subclass specificity, inter-subclass specificity and class-wide cross-reactivity, suggesting some conserved epitopes, including two conserved arginines, are shared by the class 5 adhesins. However, the cross-reactive mAbs had functional activities limited to CFA/I, CS17 or CS1 strains, suggesting the breadth of functional activity of the mAbs was more restricted than the repertoire of cross-reactivity measured by ELISA. The results implicate multivalent adhesin-based ETEC vaccines or prophylactics need more than one active component to reach broad protection.
