Group B Streptococcus (GBS) causes serious infection in neonates and is an important target of vaccine development. Zwitterionic polysaccharides (ZPS), obtained through chemical introduction of positive charges into anionic polysaccharides (PS) from GBS, have the ability to activate human and mouse antigen presenting cells (APCs) through toll-like receptor 2 (TLR2).To generate a polysaccharide vaccine with antigen (Ag) and adjuvant properties in one molecule, we have conjugated ZPS with a carrier protein. ZPS-glycoconjugates induce higher T-cell and Ab responses to carrier and PS, respectively, compared to control PS-glycoconjugates made with the native polysaccharide form. The increased immunogenicity of ZPS-conjugates correlates with their ability to activate dendritic cells (DCs). Moreover, protection of mothers or neonate offspring from lethal GBS challenge is better when mothers are immunized with ZPS-conjugates compared to immunization with PS-conjugates. In TLR2 knockout mice, ZPS-conjugates lose both their increased immunogenicity and protective effect after vaccination. When ZPS are coadministered as adjuvants with unconjugated tetanus toxoid (TT), they have the ability to increase the TT-specific antibody titer. In conclusion, glycoconjugates containing ZPS are potent vaccines. They target Ag to TLR2-expressing APCs and activate these APCs, leading to better T-cell priming and ultimately to higher protective Ab titers. Thus, rational chemical design can generate potent PS-adjuvants with wide application, including glycoconjugates and coadministration with unrelated protein Ags.adjuvant ͉ dendritic cell ͉ Group B Streptococcus C lassically, capsular polysaccharides (PS) from bacteria are considered to be T-independent Ags (1) able to activate B cells directly, without a contribution of help by CD4 ϩ T cells. Therefore, the immune response to PS fails to induce significant and prolonged titers of antibody with high avidity in infants and persistent Agspecific memory B cells in adults. For this reason, in vaccines, PS are mostly used conjugated with a carrier protein that provides T-cell help and consequently immunological memory (2). Glycoconjugate vaccines against the Gram-positive bacterium Group B Streptococcus (GBS) have been shown to confer serotype specific protection in mice and have been tested in clinical trials (3). In humans, addition of alum to the vaccine formulation did not further increase the immune response induced (4). In contrast, in animal models, adsorption to Al(OH) 3 (alum) enhances the immunogenicity of the glycoconjugate (5, 6) which may be explained by the possibility that animals are more naive to GBS than humans. Moreover, a number of commercially available glycoconjugate vaccines, such as those against Meningococcus C, Haemophilus influenza, and the 7-valent Pneumococcus vaccine, use alum or aluminium phosphate as an adjuvant. Thus, the combination of glycoconjugates with adjuvants likely generates potent vaccines, able to activate APCs and induce strong Ag-specific T and B c...
