Among them, P10A7 and P5C7 also showed strong or moderate functional cross-reactivity to the heterologous CS17+ ETEC strain WS6788A, suggesting the three residues (R67, S86, and R181) identified by P10A7 and P5C7 were functional epitope residues shared between CfaE and CsbD. a fimbrial tip adhesin. However, sequence variability among the class 5 adhesins may Cinnamic acid hinder the generation of cross-protective antibodies. To better understand practical epitopes of the class 5 adhesins and their ability to induce intraclass antibody reactions, we produced 28 antiadhesin monoclonal antibodies (MAbs) to representative adhesins CfaE, CsbD, and CotD, respectively. We identified the MAb cross-reactivities, localized the epitopes, and measured functional activities as potency in inhibition of hemagglutination induced by class 5 fimbria-bearing ETEC. The MAbs reactivities to a panel of class 5 adhesins in enzyme-linked immunosorbent assays (ELISAs) exposed several reactivity patterns, including individual adhesin specificity, intrasubclass specificity, intersubclass specificity, and class-wide cross-reactivity, suggesting that some conserved epitopes, including two conserved arginines, are shared by the class 5 adhesins. However, the cross-reactive MAbs experienced functional activities limited to strains expressing colonization element antigen I (CFA/I), coli surface antigen 17 (CS17), or CS1, suggesting the Cinnamic acid breadth of practical activities of the MAbs was more restricted than the repertoire of cross-reactivities measured by ELISA. The results imply that multivalent adhesin-based ETEC vaccines or prophylactics need more than one active component to reach broad safety. KEYWORDS: ETEC, enterotoxigenic (ETEC) is definitely a major cause of watery diarrhea among travelers and young children in low to middle income countries (1,C3). The adherence of ETEC to sponsor intestinal cells via colonization factors (CFs) and the subsequent secretion of enterotoxins are the major initial methods in its pathogenesis, and thus, much of the current efforts to develop an ETEC vaccine have focused primarily on these virulence factors (4). While the development of a vaccine against human being ETEC has been complicated from the serological diversity of more than 25 known CFs (5), many of these fimbriae are closely related, based on their sequence similarities (6). The ETEC class 5 fimbrial family consists of eight members divided into three subclasses, 5a (colonization element antigen I [CFA/I], coli surface antigen 4 [CS4], and CS14), 5b (CS1, CS17, and CS19), and 5c (CS2) Cinnamic acid (5, 7), some of which are highly common in human-pathogenic isolates (8). In the past 2 decades, studies on these class 5 fimbriae have exposed their molecular assembly and functional parts. Specifically, each class 5 fimbria is composed of more than 1,000 pilus major subunits and one or two tip-localized small subunits (9,C11), which are noncovalently connected through a donor strand complementation mechanism utilized by many other Gram-negative bacterial pili (10, 12, 13). Our group as well as others have demonstrated the minor subunits of the class 5 fimbriae are essential parts for Cinnamic acid the bacterial adherence, functioning as fimbrial tip adhesins. This is supported by findings that a solitary point mutation, a change of R to A at Cinnamic acid position 181 (R181A), in CooD (CS1 adhesin) and CfaE (CFA/I adhesin) abolished homologous bacterial binding to erythrocytes and intestinal cells (14,C16) and that rabbit antibodies to CfaE reduced the binding of CFA/I-expressing (CFA/I+) ETEC to Caco-2 cells and inhibited hemagglutination induced by CFA/I+ ETEC (7, 15). Furthermore, the antibodies to the N-terminal half of CfaE were more effective in obstructing the CFA/I+ ETEC binding to the sponsor cells than were the antibodies to the C-terminal half of the adhesin (7). In addition, human being monoclonal antibodies (MAbs) to the putative receptor binding site of CfaE not only fully inhibited hemagglutination, diminished ETEC adhesion to Caco-2 cells, and reduced homologous ETEC colonization in the adult mouse model (17) but also shown efficacy inside a nonhuman primate model when challenged with the H10407 strain (18). Importantly, we have shown that antibodies Mouse monoclonal antibody to Protein Phosphatase 1 beta. The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1(PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in theregulation of a variety of cellular processes, such as cell division, glycogen metabolism, musclecontractility, protein synthesis, and HIV-1 viral transcription. Mouse studies suggest that PP1functions as a suppressor of learning and memory. Two alternatively spliced transcript variantsencoding distinct isoforms have been observed against CfaE are protecting against.