title: Investigating the candidacy of a lipoteichoic acid-based glycoconjugate as a vaccine to combat Clostridium difficile infection.
abstract: A lipoteichoic acid has recently been shown to be conserved in the majority of strains from Clostridium difficile and as such is being considered as a possible vaccine antigen. In this study we examine the candidacy of the conserved lipoteichoic acid by demonstrating that it is possible to elicit antibodies against C. difficile strains following immunisation of rabbits and mice with glycoconjugates elaborating the conserved lipoteichoic acid antigen. The present study describes a conjugation strategy that utilises an amino functionality, present at approximately 33 % substitution of the N-acetyl-glucosamine residues within the LTA polymer repeating unit, as the attachment point for conjugation. A maleimide-thiol linker strategy with the maleimide linker on the carboxyl residues of the carrier protein and the thiol linker on the carbohydrate was employed. Immunisation derived antisera from rabbits and mice, recognised all strains of C. difficile vegetative cells examined, despite an immune response to the linkers also being observed. These sera recognised live cells in an immunofluorescence assay and were also able to recognise the spore form of the bacterium. This study has illustrated that the LTA polymer is a highly conserved surface polymer of C. difficile that is easily accessible to the immune system and as such merits consideration as a vaccine antigen to combat C. difficile infection.
authors: Vaccine Program, Human Health Therapeutics Portfolio, National Research Council, Ottawa, ON, K1A 0R6, Canada, Andrew.Cox@nrc-cnrc.gc.ca.
authors: Andrew D
authors: AD
authors: Cox
authors: Frank
authors: F
authors: St Michael
authors: Annie
authors: A
authors: Aubry
authors: Chantelle M
authors: CM
authors: Cairns
authors: Philippa C R
authors: PC
authors: Strong
authors: Alexander C
authors: AC
authors: Hayes
authors: Susan M
authors: SM
authors: Logan
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000737:chemistry / Q000276:immunology*; D016360:Clostridioides difficile / Q000276:immunology*; D007114:Immunization; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D011817:Rabbits; D013682:Teichoic Acids / Q000737:chemistry / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D018074:Vaccines, Conjugate; C009900:lipoteichoic acid
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