Glycoconjugate vaccines are composed of a weak antigen (containing only a B-cell epitope), generally a microbial poly- or oligosaccharide, covalently linked to a carrier protein as a source of T-cell epitopes1. Chemical conjugation of polysaccharides to protein carriers allows switching from T-cell independent to T-cell-dependent response, leading to immunological memory and boosting effect. Aim of our work is to determine if a protein can be used both as antigen and as carrier.
While classic procedures for conjugation (reductive amination, amide bond formation, etc.) rely on the random reaction of the polysaccharide to the amines of the carrier protein, recently novel conjugation methods enabling site specific installation of a ligand onto a protein are emerging2. Site specific conjugation, besides proving more homogeneous biomolecules as vaccine candidates, could aid to preserve the immunogenicity of the protein. Group BStreptococcus(GBS), is a leading cause of severe bacterial infections in early 3 months of life among newborns and of septic morbidity among mothers3. GBS is also an important cause of morbidity and mortality among non-pregnant adults, particularly among old people and adults with underlying medical conditions. All GBS strains possess a capsular polysaccharide (CPS) on their surface which is a major virulence factor. Monovalent conjugate vaccines have been prepared against serotypes Ia, Ib, II, III, IV, V, VI, VII ,VIII and effectiveness demonstrated in animal models3.
Recently, it has been demonstrated that GBS pilus proteins, besides being important structures in bacterial adhesion and invasion, seem to be more conserved than those of other Gram-positive bacteria4. We are developing conjugates of GBS polysaccharides using pilus proteins as carriers. Use of a protein carrier will allow us to explore their double role both as carrier as well as antigen. Concomitantly, the impact of differing conjugation chemistries and coupling sites on protective epitopes is being evaluated.
1. Expert Opin.Drug Discovery2011,6 (10), 1045.
2. Peptide Science2010, 94(1), 95.
3. Pure Appl. Chem.1984,56, 893.
4.Nature Reviews2006,4, 509
