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Inal, Jameel and Tintor, Erica Muriana (2026) Development of a novel mucosal multi-epitope subunit vaccine against Clostridioides difficile, incorporating recombinant outer membrane vesicles and spores. Medical Hypotheses, 211 (111960). pp. 1-5. ISSN 1532-2777
Clostridioides difficile infection (CDI) remains a major global healthcare challenge, driven by antibiotic-induced gut dysbiosis, high recurrence rates, and the absence of an effective vaccine. Current toxoid-based vaccine strategies have failed to prevent intestinal colonization and initial infection, underscoring the need for approaches that induce robust mucosal immunity. Here, we propose a novel mucosal multi-epitope subunit vaccine (MEV) targeting both vegetative cells and spores of C. difficile that could possibly block colonization, transmission, and disease. The vaccine combines two complementary delivery platforms: recombinant outer membrane vesicles (OMVs) from Escherichia coli expressing the colonization factors FliC and Cwp2 for intranasal administration, and genetically engineered Bacillus subtilis spores displaying the spore protein CdeC and the surface lipoprotein CD0873, for oral delivery. This dual-route strategy is designed to stimulate strong mucosal secretory IgA alongside systemic IgG responses. Both OMVs and spores possess intrinsic adjuvant properties, enhancing antigen presentation and immune activation. In a murine CDI model, vaccine efficacy can be assessed by bacterial clearance, histopathology, and cytokine profiling. By targeting surface-expressed antigens rather than toxins alone, this MEV has the potential, we hypothesize, to prevent colonization and recurrence, offering a scalable platform for vaccines against other enteric pathogens.
Available under License Creative Commons Attribution 4.0.
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