Abstract
Primary examples in vaccine design have shown good levels of carbohydrate-specific antibody generation when raised using extracted or fully synthetic capsular polysaccharide glycans covalently coupled to a protein carrier. Herein, we cover recent clinical developments of carbohydrate-based vaccines and describe how novel cutting-edge methodology for the total synthesis of oligosaccharides and for the precise placement of carbohydrates at pre-determined sites within a protein may be used to further improve the safety and efficacy of glycovaccines.
Highlights
Carbohydrate-based vaccines hold great promise for a number of diseases.[1]
Different variables can in uence the immunogenicity of the glycoconjugate: some of them are correlated to the sugar hapten, such as chain length, non-reducing end residue, charge, or presence of branching points; others depend on the conjugation chemistry and the type of spacer employed, which could direct the immunoresponse away from the sugar antigen, and the number of sugar moieties attached to the protein
Glycoproteins are the centre of many vaccines that are either in the clinic or in advanced clinical trials.[1]
Summary
Carbohydrate-based vaccines hold great promise for a number of diseases.[1]. The chemical nature of carbohydrate antigens presents a number of challenges with respect to inducing speci c, protective antibodies: carbohydrates are poorly immunogenic, and in addition to that, carbohydrate-speci c antibodies typically have low affinity (with KD values in the micromolar range for monovalent interactions) compared with protein-speci c antibodies (with KD values in the nanomolar range). Bacterial polysaccharides are high molecular weight molecules that, unlike proteins, are T-cell independent antigens and cannot be processed by antigen-presenting cells They rather trigger B-cell responses by cross-linking the B-cell receptor, without any Major Histocompatibility Complex class II (MHCII) CD4+ T-cell interaction. A new mode of action for carbohydrate-based vaccines has been proposed in which T-cells can recognize a pure carbohydrate epitope regardless of the peptide to which they are linked.[5] The carbohydrate epitope bound to a peptide that results from endolysosomal processing of a Group B Streptococcus type III polysaccharide conjugated to a protein carrier, was shown to bind MHCII and to stimulate carbohydrate-speci c CD4+ T-cell clones. More complex constructs based on multivalent exposition of the haptens or incorporation of a covalently linked adjuvant have been recently suggested and will be discussed below
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