4.7 Review

Mucosal Vaccination Strategies against Clostridioides difficile Infection

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Summary: Clostridioides difficile produces up to three different toxins, which play a key role in the pathogenesis of colon infection. In this Review, Kordus, Thomas, and Lacy discuss the structure and function of these toxins and how this information guides new therapeutic approaches. Understanding the mechanisms of host-toxin interactions provides a foundation for developing novel strategies for the treatment and prevention of C. difficile infection.

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Summary: This study investigated the use of non-toxigenic Clostridioides difficile (NTCD) as a vector to induce antibodies that block the adherence of C. difficile to epithelial cells in the first stage of pathogenesis. The results showed that oral immunization with the T7-0873 strain successfully induced intestinal antibodies that significantly reduced the adhesion of toxigenic C. difficile to Caco-2 cells.

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Genomic and Phenotypic Characterization of the Nontoxigenic Clostridioides difficile Strain CCUG37785 and Demonstration of Its Therapeutic Potential for the Prevention of C. difficile Infection

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Summary: Symptoms of Clostridioides difficile infection (CDI) are mainly caused by two toxins, TcdA and TcdB. The engineered strain CCUG37785 shows potential as an oral mucosal vaccine carrier against CDI, providing protection and treatment against the infection.

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Development of an Effective Nontoxigenic Clostridioides difficile-Based Oral Vaccine against C. difficile Infection

Shaohui Wang et al.

Summary: In this study, immunodominant fragments of TcdA and TcdB (Tcd169) were expressed in a nontoxigenic C. difficile strain, generating a promising oral/mucosal vaccine candidate against CDI. Importantly, sera raised against Tcd169 protein showed significant cross-reactivity with FliC/FliD and two surface layer proteins (SlpA and Cwp2), which are involved in C. difficile adhesion/colonization. Oral immunizations with the vaccine candidate provided effective protection against C. difficile infection in mice.

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Safety, immunogenicity, and efficacy of a Clostridioides difficile toxoid vaccine candidate: a phase 3 multicentre, observer-blind, randomised, controlled trial

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Summary: A phase 3 multicentre, observer-blind, randomised, controlled trial was conducted to evaluate the efficacy, immunogenicity, and safety of a toxoid vaccine candidate for Clostridioides difficile infection. However, the study was terminated after showing that the bivalent C difficile toxoid vaccine did not prevent C difficile infection, leading to the discontinuation of its clinical development.

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Colonisation Factor CD0873, an Attractive Oral Vaccine Candidate against Clostridioides difficile

Cansu Karyal et al.

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Mimicking Native Display of CD0873 on Liposomes Augments Its Potency as an Oral Vaccine against Clostridioides difficile

Cansu Karyal et al.

Summary: Mucosal vaccination aims to prevent infection by inducing secretory IgA antibodies, with the study showing that antigens displayed on liposomes drive a stronger antibody response. The development of CD0873-MalLipo holds promise for a novel oral vaccine platform inducing significant neutralizing activity.

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Summary: Clostridioides difficile, formerly known as Clostridium difficile, is the causative agent of C. difficile infections, which pose challenges in healthcare settings. Antibiotic-induced dysbiosis allows C. difficile colonization in the gut. Phage infection offers potential new treatment strategies against C. difficile infections.

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