Schistosomiasis is an acute and chronic disease caused by blood dwelling parasitic trematodes of the genus Schistosoma, and it is classified as the second most socioeconomically devastating... Show moreSchistosomiasis is an acute and chronic disease caused by blood dwelling parasitic trematodes of the genus Schistosoma, and it is classified as the second most socioeconomically devastating parasitic disease, second only to malaria. Currently the wormload is determined by the Kato-Katz method, which is not always reliable. In order to prepare diagnostic tools able to capture specific anti-carbohydrate antibodies or develop conjugate vaccines targeting these carbohydrate structures, sufficient amounts of well-defined fragments are needed. This thesis describes the synthesis of several glycans of these glycans present on the S. mansoni parasite, focusing mainly on the Circulating Anodic Antigen (CAA) and glycans bearing the unique α-(1-2)-L-Fucose-α-(1-2)-L-Fucose motifs. These glycans have been attached to gold nanoparticles and these particles were screened against several monoclonal antibodies and sera of individuals suffering from schistosomiasis. Show less
Glycoconjugate vaccines are composed of microbial poly- or oligosaccharides covalently linked to a carrier protein. In the absence of structural information, long poly- or oligosaccharides... Show moreGlycoconjugate vaccines are composed of microbial poly- or oligosaccharides covalently linked to a carrier protein. In the absence of structural information, long poly- or oligosaccharides extracted from bacteria are employed to cover all relevant glyco epitopes and elicit an effective immune response. The comprehension of the structural basis for the immune recognition of carbohydrate antigens and the elucidation of minimal epitopes is key to understand their mechanism of action and support the rational design of modern glycoconjugate vaccines.Group B streptococcus (GBS) is a Gram-positive bacterium, cause of infections in pregnant women and newborns, whose capsular polysaccharide (CPS) is a major virulence factor.A small library of GBS glycans from serotypes Ia, Ib and III CPSs was synthesized. These oligosaccharides were used to model the conformational preferences of the corresponding CPS and to characterize the interactions to protective anti PS monoclonal antibodies. Conjugation to carrier proteins of the most promising fragments and evaluation in vivo of the obtained glycoconjugates showed that a hexasaccharide corresponding to the minimal structural epitope of GBS III was able to elicit anti PSIII functional IgGs. Overall, the findings described in this Thesis open the path to the design of GBS vaccines based on synthetic oligosaccharides. Show less
The glycosylation, the reaction which forms a bond between sugar molecules (the donor and the acceptor), is the central reaction in carbohydrate chemistry. Despite tremendous advances in... Show more The glycosylation, the reaction which forms a bond between sugar molecules (the donor and the acceptor), is the central reaction in carbohydrate chemistry. Despite tremendous advances in the past decades, however, the glycosylation reaction remains relatively poorly understood. Especially the formation of 1,2-cis glycosidic linkages remains a significant challenge. This thesis describes an investigation of the influence of reactivity and selectivity of several classes of carbohydrate donors and –acceptors on the selectivity in glycosylation reactions. Special emphasis was placed on the influence of protecting groups on the donor, and nucleophilicity of the acceptor, two major factors that play a tremendous role in the outcome of a glycosylation reaction. The obtained knowledge has been applied in the synthesis of complex carbohydrate molecules, native to pathogens such as Staphylococcus aureus, of which antibiotic-resistant forms such as MRSA present significant danger in hospitals, and the parasite Schistosoma mansoni, causative agent of the neglected tropical disease schistosomiasis. The synthesis of these molecules can play a part in the development of vaccines targeted against these pathogens. Show less
