2016
DOI: 10.1038/ncomms11224
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Abstract: Synthetic cell-surface glycans are promising vaccine candidates against Clostridium difficile. The complexity of large, highly antigenic and immunogenic glycans is a synthetic challenge. Less complex antigens providing similar immune responses are desirable for vaccine development. Based on molecular-level glycan–antibody interaction analyses, we here demonstrate that the C. difficile surface polysaccharide-I (PS-I) can be resembled by multivalent display of minimal disaccharide epitopes on a synthetic scaffol… Show more

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Cited by 60 publications
(68 citation statements)
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“…Glycan arrays of poly-and monoclonal antibodies from mice immunized with PS-I repeating unit pentasaccharide revealed cross-reactivity to a disaccharide minimal epitope, albeit with considerably different mAb dissociation constants of 163-245 nM and 5.9-37.5 μM for penta-and disaccharide, respectively. Further immunizations proved the disaccharide able to elicit antipentasaccharide antibodies showing the vaccine antigen potential of the smaller and synthetically easier accessible glycan (128,142).…”
Section: Biomarkers and Vaccinesmentioning
confidence: 99%
See 1 more Smart Citation
“…Glycan arrays of poly-and monoclonal antibodies from mice immunized with PS-I repeating unit pentasaccharide revealed cross-reactivity to a disaccharide minimal epitope, albeit with considerably different mAb dissociation constants of 163-245 nM and 5.9-37.5 μM for penta-and disaccharide, respectively. Further immunizations proved the disaccharide able to elicit antipentasaccharide antibodies showing the vaccine antigen potential of the smaller and synthetically easier accessible glycan (128,142).…”
Section: Biomarkers and Vaccinesmentioning
confidence: 99%
“…On a general note, carbohydrates alone are usually T cell-independent antigens that induce high levels of immunoglobulin M (IgM) and low levels of IgG antibodies but do not induce affinity maturation (6,126). Although antibodies with nanomolar affinities can be obtained with glycoconjugate vaccines, many antiglycan antibodies bind in the micromolar range (6,127,128). With its 10 binding sites, IgM can engage in more multivalent interactions than IgG, which is a bivalent binder.…”
Section: Biomarkers and Vaccinesmentioning
confidence: 99%
“…Large glycans are highly antigenic and immunogenic, which is a challenge for designing a selective vaccine, so smaller and less complex antigens which provide a similar immune responses are desirable for vaccine development. Broecker et al [41] demonstrated that disaccharides multivalently linked on a synthetic OAA scaffold were highly antigenic and induced antibodies to larger C. difficile surface Polysaccharide-I (PS-I) glycans in mice. Molecular insights into interactions of purified monoclonal antibodies (mAbs) with mono-and multivalent glycans involved SPR, saturation transfer difference (STD)-NMR and ITC experiments.…”
Section: Carbohydrate/antibody Interactionsmentioning
confidence: 99%
“…Molecular insights into interactions of purified monoclonal antibodies (mAbs) with mono-and multivalent glycans involved SPR, saturation transfer difference (STD)-NMR and ITC experiments. The binding strengths of the mAbs to PS-I glycans (shown in Figure 3) were determined by SPR [41]. K D values to glycan 1 were around 200 nanomolar, binding to 2 was around 15 micromolar, and binding to 3 was around 15 micromolar.…”
Section: Carbohydrate/antibody Interactionsmentioning
confidence: 99%
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