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Colonization factor antigen CS2 (CS2) is a fimbrial adhesin expressed on the surface of Enterotoxigenic Escherichia coli (ETEC), which is a primary cause of diarrhea in children in low-income countries and travelers (Qadri et al., 2005, Lancet). CS2 is a member of the CFA/II group of colonization factors and is composed of major subunits, typically the CotA protein, which assemble into hair-like appendages (UniProt: P0CK95). Its primary biological function is to facilitate the attachment of ETEC to the human intestinal mucosa, allowing the bacteria to colonize the small intestine and deliver enterotoxins that cause fluid secretion (Svennerholm, 2010, Expert Rev Vaccines). As a critical virulence factor, CS2 is a major target for vaccine development, particularly in multivalent oral inactivated vaccines like ETVAX (Lundgren et al., 2014, Vaccine). These vaccines aim to elicit a robust mucosal IgA response that blocks the adhesin's ability to bind to host receptors, thereby preventing infection. Therapeutic strategies also include the development of monoclonal antibodies and small-molecule inhibitors designed to disrupt the adhesion process (Fleckenstein et al., 2014, J Clin Invest). Challenges in targeting CS2 include the high degree of antigenic diversity among ETEC strains and the necessity for broad-spectrum protection across various colonization factors. Despite these challenges, CS2 remains a cornerstone of ETEC vaccine research due to its high prevalence in clinical isolates.
Induction of neutralizing antibodies (primarily secretory IgA) that bind to the CS2 fimbriae, preventing bacterial attachment to host intestinal receptors and subsequent colonization.
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