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F4 fimbriae (formerly K88) are filamentous surface appendages of enterotoxigenic Escherichia coli (ETEC) that mediate bacterial attachment to the small intestinal epithelium of piglets (Van den Broeck et al., 2000). They are composed of a major subunit, FaeG, which acts as the primary adhesin, and several minor subunits including FaeC, FaeF, FaeH, and FaeI (Moonens et al., 2015). F4 fimbriae exist in three antigenic variants (F4ab, F4ac, F4ad) that recognize different host receptors, such as MUC4 and aminopeptidase N (APN) (Xia et al., 2015). This adhesion is a critical first step in ETEC pathogenesis, leading to colonization and subsequent release of enterotoxins that cause severe diarrhea and mortality in neonatal and weaned pigs (Zhang et al., 2012). Consequently, F4 fimbriae are primary targets for the development of oral and injectable vaccines, such as Coliprotec F4 and Gletvax 6 (EMA, 2015). Additionally, anti-adhesive agents like specific antibodies (e.g., K609) and receptor analogs (e.g., lactose) are being explored to block bacterial colonization by preventing fimbriae-mediated attachment (Moonens et al., 2015).
Active immunization to induce mucosal IgA and IgG antibodies; Passive immunization via oral administration of anti-F4 antibodies; Anti-adhesion by blocking the FaeG subunit binding to host receptors; Competitive inhibition using receptor analogs.
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