Defined neoglycoproteins as candidate vaccines against Streptococcus pneumoniae type 3

Abstract

Several bacteria that are surrounded by a polysaccharide coat can cause severe diseases like meningitis, pneumonia and otitis media, especially in young children. Against the bacterium Streptococcus pneumoniae, a polysaccharide vaccine exists. However, it does not effectively protect high-risk groups such as young children. In contrast, neoglycoprotein vaccines, containing carbohydrate material derived from the polysaccharide capsule conjugated to a protein, have been shown to afford protection, also in the high-risk groups. The immunological mechanism of this type of vaccines remains unclear. To investigate this, neoglycoproteins with a defined structure have to become available. In this thesis, neoglycoproteins have been prepared according to the structure of the capsular polysaccharide (CPS) of S. pneumoniae type 3. Both chemical synthesis and partial acid hydrolysis of the CPS have been carried out to obtain defined oligosaccharides with a unique structure. Neoglycoproteins were prepared using the synthetic carbohydrates and their immunogenicity in mice was studied. Eventually, the use of this type of defined antigens will increase the insight in the immune response of conjugate vaccines and will hopefully lead to the development of more efficient vaccines.