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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.

Since its commercial release, Zyderm collagen implant has been used to treat more than 200,000 subjects in the United States for soft-tissue contour defects and more than 250,000 patients internationally (including the United States). Approximately 3 percent of subjects' skin tested with Zyderm collagen experience localized hypersensitivity reactions to collagen, whereas approximately 1 percent of treated patients demonstrate symptoms of hypersensitivity at treatment sites. Of the latter treatment responses reported since the conclusion of clinical trials with Zyderm, 56 percent occurred following the first treatment, 28 percent following the second, 10 percent following the third, and 6 percent following subsequent exposures. The data indicate that most patients receive a median of three treatments (mean = 4.4) with Zyderm collagen, but most patients who are likely to develop sensitivity to Zyderm collagen appear to respond immunologically to the test implant or first treatment exposure. Examining these treatment responses, 45 percent of the patients reported an onset of symptoms within 10 days and 22 percent at more than 30 days following the last treatment with Zyderm collagen. Erythema was the sole symptom in 24 percent of cases, whereas erythema plus induration comprised an additional 42 percent. Antibodies against Zyderm collagen were detected in the sera of 88 percent of these subjects using an ELISA, but no reactivity was observed against human collagen. Sera from patients reporting only systemic symptoms were not found to have anticollagen antibodies. These data suggest that the relative risk of a hypersensitivity reaction to Zyderm collagen does not increase with multiple exposures, since patients who are going to develop an immune response to bovine collagen react with greatest frequency to initial injections of collagen. In animal models, Zyderm collagen was shown to be less immunogenic than other medical devices which are composed of bovine collagen. Specifically, comparative studies were conducted in which Zyderm collagen and hemostatic agents were implanted in the guinea pig subcutaneum: sera from animals treated with collagen-derived hemostatic devices possessed significant levels of anti-implant antibodies (titers greater than 640), whereas animals treated with Zyderm collagen mounted minimal responses (titers less than 40). Additional studies were conducted in which implant materials were compared in a guinea pig parietal (bony defect) model and in a rabbit hemostasis model: in both, Zyderm collagen demonstrated lower immunogenicity than commercial bovine collagen hemostatic agents. Histologic results from these studies showed Zyderm