Comparison of polysaccharide glycoconjugates as candidate vaccines to combat Clostridiodes (Clostridium) difficile

Cox, Andrew D.; Michael, F St; Aubry, Annie; Strong, Philippa C. R.; Hayes, Alexander C.; Logan, Susan M.

doi:10.1007/s10719-020-09937-9

Cited by 6 publications

(2 citation statements)

References 31 publications

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“…Table 1 shows that the percentage nucleotide and amino acid identities of these vaccine candidates are 99%–100%, except for SLpA. Promising non-protein antigens such as oligosaccharides [ 55 ], lipoteichoic acids, and carbohydrate polymers [ 56 , 57 ] are also common in the cell walls of NTCD and TCD but were not included in this analysis due to the complexity of numerous genes required for their biosynthesis.…”

Section: Resultsmentioning

confidence: 99%

Towards Development of a Non-Toxigenic Clostridioides difficile Oral Spore Vaccine against Toxigenic C. difficile

et al. 2022

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Clostridioides difficile is an opportunistic gut pathogen which causes severe colitis, leading to significant morbidity and mortality due to its toxins, TcdA and TcdB. Two intra-muscular toxoid vaccines entered Phase III trials and strongly induced toxin-neutralising antibodies systemically but failed to provide local protection in the colon from primary C. difficile infection (CDI). Alternatively, by immunising orally, the ileum (main immune inductive site) can be directly targeted to confer protection in the large intestine. The gut commensal, non-toxigenic C. difficile (NTCD) was previously tested in animal models as an oral vaccine for natural delivery of an engineered toxin chimera to the small intestine and successfully induced toxin-neutralising antibodies. We investigated whether NTCD could be further exploited to induce antibodies that block the adherence of C. difficile to epithelial cells to target the first stage of pathogenesis. In NTCD strain T7, the colonisation factor, CD0873, and a domain of TcdB were overexpressed. Following oral immunisation of hamsters with spores of recombinant strain, T7-0873 or T7-TcdB, intestinal and systemic responses were investigated. Vaccination with T7-0873 successfully induced intestinal antibodies that significantly reduced adhesion of toxigenic C. difficile to Caco-2 cells, and these responses were mirrored in sera. Additional engineering of NTCD is now warranted to further develop this vaccine.

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Section: Resultsmentioning

confidence: 99%

Towards Development of a Non-Toxigenic Clostridioides difficile Oral Spore Vaccine against Toxigenic C. difficile

et al. 2022

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“…Much attention has been given to polysaccharide-based CD vaccine formulations in previous years [ 56 ]; however, there is still no such vaccine on the market. Cox et al, showed that lipoteichoic acid (LTA) and PS-II polysaccharides are highly conserved polymers of CD, visible on the bacterial surface and easily accessible to the immune system [ 57 ]. LTA alone was able to induce an immune response; however, PS-II needed a carrier protein for proper presentation.…”

Section: Targeting CD Surface Glycopolymersmentioning

confidence: 99%

Non-Toxin-Based Clostridioides difficile Vaccination Approaches

2023

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Clostridioides difficile (CD) is a Gram-positive, anaerobic bacterium that infects mainly hospitalized and elderly people who have been treated with long-term antibiotic therapy leading to dysbiosis. The deteriorating demographic structure and the increase in the number of antibiotics used indicate that the problem of CD infections (CDI) will continue to increase. Thus far, there is no vaccine against CD on the market. Unfortunately, clinical trials conducted using the CD toxin-based antigens did not show sufficiently high efficacy, because they did not prevent colonization and transmission between patients. It seems that the vaccine should also include antigens found in the bacterium itself or its spores in order not only to fight the effects of toxins but also to prevent the colonization of the patient. This literature review summarizes the latest advances in research into vaccine antigens that do not contain CD toxins.

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Serum IgM antibody response to Clostridioides difficile polysaccharide PS-II vaccination in pony foals

Arroyo

Hodgins²,

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et al. 2022

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Comparison of polysaccharide glycoconjugates as candidate vaccines to combat Clostridiodes (Clostridium) difficile

Cited by 6 publications

References 31 publications

Towards Development of a Non-Toxigenic Clostridioides difficile Oral Spore Vaccine against Toxigenic C. difficile

Towards Development of a Non-Toxigenic Clostridioides difficile Oral Spore Vaccine against Toxigenic C. difficile

Non-Toxin-Based Clostridioides difficile Vaccination Approaches

Serum IgM antibody response to Clostridioides difficile polysaccharide PS-II vaccination in pony foals

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