Immunology of carbohydrate antigens related to Streptococcus pneumoniae infection : synthesis of a glycolipid construct

Carbohydrates in the form of capsular polysaccharides are the major components on the surface of bacteria, and are important virulence factors of invading bacteria. Immunity against these components confers protection against the infectious disease. However, there are several problems associated to the development of vaccines based on saccharidic antigens. Bacterial polysaccharides are poorly immunogenic T-independent antigens, and they are able to induce only the release of low affinity antibody from B lymphocytes, but not their differentiation.1 The T-lymphocyte independent nature of a polysaccharide may be overcome by conjugating the native or depolymerized polysaccharide to a carrier protein. In a similar way, the conjugation to an immunoadjuvant could lead to a construct able to stimulate a sustainable antibody response. Recently, lipoproteins, i.e. Pam3Cys, have been shown as potent activators of B-lymphocytes and macrophages,2 and thus represent a promising tool for the development of conjugated vaccines. Herein, the synthesis of a glycoconjugate where the repeating unit of Streptococcus pneumoniae (SP) type 19F capsular polysaccharide is linked to a Pam3CysSer residue through an amino propyl linker will be presented as a case study. The final aim is to evaluate the influence of the lipopeptide on the immune response towards SP, and if antigen specific antibodies can be elicited with low molecular weight conjugates of Pam3CysSer with a saccharide-based hapten