title: Vaccination against Clostridium difficile using toxin fragments: Observations and analysis in animal models.
abstract: Clostridium difficile is a major cause of antibiotic associated diarrhea. Recently, we have shown that effective protection can be mediated in hamsters through the inclusion of specific recombinant fragments from toxin A and B in a systemically delivered vaccine. Interestingly while neutralizing antibodies to the binding domains of both toxin A and B are moderately protective, enhanced survival is observed when fragments from the glucosyltransferase region of toxin B replace those from the binding domain of this toxin. In this addendum, we discuss additional information that has been derived from such vaccination studies. This includes observations on efficacy and cross-protection against different ribotypes mediated by these vaccines and the challenges that remain for a vaccine which prevents clinical symptoms but not colonization. The use and value of vaccination both in the prevention of infection and for treatment of disease relapse will be discussed.
authors.affiliation: Institute of Infection, Immunity, and Inflammation; College of Medicine, Veterinary and Life Sciences; University of Glasgow; Glasgow, UK.
authors.forename: Janice
authors.initials: J
authors.lastname: Spencer
authors.affiliation: Novartis Vaccines and Diagnostics; Siena, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Leuzzi
authors.affiliation: Institute of Infection, Immunity, and Inflammation; College of Medicine, Veterinary and Life Sciences; University of Glasgow; Glasgow, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Buckley
authors.affiliation: Institute of Infection, Immunity, and Inflammation; College of Medicine, Veterinary and Life Sciences; University of Glasgow; Glasgow, UK.
authors.forename: June
authors.initials: J
authors.lastname: Irvine
authors.affiliation: Institute of Infection, Immunity, and Inflammation; College of Medicine, Veterinary and Life Sciences; University of Glasgow; Glasgow, UK.
authors.forename: Denise
authors.initials: D
authors.lastname: Candlish
authors.affiliation: Novartis Vaccines and Diagnostics; Siena, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Scarselli
authors.affiliation: Institute of Infection, Immunity, and Inflammation; College of Medicine, Veterinary and Life Sciences; University of Glasgow; Glasgow, UK.
authors.forename: Gillian R
authors.initials: GR
authors.lastname: Douce
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D016360:Clostridioides difficile / Q000276:immunology* / Q000378:metabolism*; D006224:Cricetinae; D003967:Diarrhea / Q000276:immunology / Q000382:microbiology; D023421:Models, Animal; D014611:Vaccination
chemical_list: D057134:Antibodies, Neutralizing; D001427:Bacterial Toxins; D001428:Bacterial Vaccines
keywords: Clostridium difficile; colonization factors; diarrhea; glucosyltransferase activity; hamster models; neutralizing antibodies; protection; toxin fragments; vaccination