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Clostridioides difficile surface antigens are a complex array of proteins and glycoproteins located on the outermost layer of the bacterium, serving as the primary interface between the pathogen and the host environment. The most prominent component is the Surface Layer Protein A (SlpA), which undergoes post-translational cleavage to form a paracrystalline S-layer that covers the entire cell surface and is essential for adhering to host intestinal epithelial cells (Kirk et al., 2017, Nature Communications). Other critical antigens include flagellar proteins like FliC and FliD, which facilitate motility and initial attachment, and various cell wall proteins (CWPs) involved in biofilm formation and immune modulation (Péchiné et al., 2018, Frontiers in Microbiology). In the context of Clostridioides difficile infection (CDI), these surface antigens are high-priority targets for prophylactic vaccines and passive immunotherapies. Unlike toxin-targeting agents that neutralize the damage caused by the infection, therapies targeting surface antigens aim to prevent the initial colonization and persistence of the bacteria in the gut (Fagan & Fairweather, 2014, Microbiology). For instance, the vaccine candidate VLA84 utilizes a recombinant fusion protein containing portions of SlpA to elicit a protective immune response. By blocking the pathogen's ability to establish a niche, these interventions potentially offer a way to reduce both primary infection rates and the high incidence of recurrence associated with CDI.
Induction of neutralizing antibodies to prevent bacterial adhesion and colonization of the intestinal epithelium; enhancement of opsonophagocytosis to clear bacterial cells.
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