Carbohydrate-based Clostridium difficile vaccines

• Published in: Expert review of vaccines Vol. 12; no. 4; pp. 421 - 431
• Main Authors: Monteiro, Mario A, Ma, Zuchao, Bertolo, Lisa, Jiao, Yuening, Arroyo, Luis, Hodgins, Douglas, Mallozzi, Michael, Vedantam, Gayatri, Sagermann, Martin, Sundsmo, John, Chow, Herbert
• Format: Journal Article
• Language: English
• Published: London Informa Healthcare 01.04.2013; Taylor & Francis; Informa; Expert Reviews Ltd
• Subjects: Animals; Animals, Domestic; Antibacterial agents; antibiotic-associated diarrhea; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antibodies, Bacterial - blood; Bacterial diseases; Bacterial diseases of the digestive system and abdomen; Bacterial vaccines; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - immunology; Biological and medical sciences; Clostridium difficile; Clostridium difficile - immunology; conjugate; Cricetinae; Disease Models, Animal; Gastroenterology. Liver. Pancreas. Abdomen; Health aspects; Human bacterial diseases; Humans; Immunoglobulin A - blood; Immunoglobulin G - blood; Infectious diseases; Medical sciences; Mice; Other diseases. Semiology; Pharmacology. Drug treatments; polysaccharide; Polysaccharides, Bacterial - immunology; PSI; PSII; PSIII; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; vaccine; Vaccines, Conjugate - administration & dosage; Vaccines, Conjugate - immunology; Canada; United States; PSII; Clostridium difficile; PSI; Clostridiales; Diarrhea; PSIII; Vaccine; Prevention; antibiotic-associated diarrhea; Immunoprophylaxis; conjugate; Antibiotic; Immunogenicity; Clostridiaceae; Bacteria; Digestive diseases; Intestinal disease; Antibacterial agent; Polysaccharide
• ISSN: 1476-0584; 1744-8395
• DOI: 10.1586/erv.13.9

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.