Carbohydrate-basedClostridium difficilevaccines

Abstract

Clostridium difficile is responsible for thousands of deaths each year and a vaccine would be welcomed, especially one that would disrupt bacterial maintenance, colonization and persistence in carriers and convalescent patients. Structural explorations at the University of Guelph (ON, Canada) discovered that C. difficile may express three phosphorylated polysaccharides, named PSI, PSII and PSIII; this review captures our recent efforts to create vaccines based on these glycans, especially PSII, the common antigen that has precipitated immediate attention. The authors describe the design and immunogenicity of vaccines composed of raw polysaccharides and conjugates thereof. So far, it has been observed that anti-PSII antibodies can be raised in farm animals, mice and hamster models; humans and horses carry anti-PSII IgA and IgG antibodies from natural exposure to C. difficile, respectively; phosphate is an indispensable immunogenic epitope and vaccine-induced PSII antibodies recognize PSII on C. difficile outer surface.

Clostridium difficilevirulence factors: Insights into an anaerobic spore-forming pathogen

“…135,136 Studies propose that CwpV promotes aggregation of the bacteria via the C-terminal repetitive domain indicating a potential role for the protein in bacterial interaction and biofilm-like formation in the host gut. 136 Polysaccharides Three cell surface polysaccharides, PSI, PSII and PSIII, have been described for vegetative cells of C. difficile, with all ribotypes, including ribotype O27, found to express PSII most abundantly (for a recent review see Monteiro et al, 2013). 137 Vaccine candidates have therefore largely centered around this carbohydrate, with the immunogenicity of different vaccines consisting of native and synthetic PSII conjugates being tested in pig, mouse and hamster models.…”

Vaccines againstClostridium difficile

“…137 Consequently, great attention has been directed in the recent years to the structural analysis of polysaccharides on the surface of C. difficile with the result of identifying 3 glycan structures, named PSI, PSII, and PSIII. 138 Among these 3 carbohydrates, PSII was found to be the more abundantly expressed by most of C. difficile ribotypes, including the hypervirulent strain NAP1/027 and other clinical isolates belonging to ribotypes 001, 018, 027, 078, and 126. 139,140 Following the discovery of PSII, it was not clear whether PSII was part of a capsule or a surface glycoprotein, or released to the external surface of the bacterium.…”

The Prospect for Vaccines to Prevent Clostridium difficile Infection

“…Further studies are underway to elucidate the role of anti-PSII adaptive immune responses against C difficile colonization. 93 C difficile spores play an important role in disease pathogenesis. Germination of spores into vegetative cells is a critical step in the lifecycle of C difficile, and interrupting this event can prevent subsequent colonization, toxin production, CDI, and disease transmission.…”