Nanoparticles as Delivery Systems for Antigenic Saccharides: From Conjugation Chemistry to Vaccine Design.

Glycoconjugate vaccines have been effective in preventing numerous bacterial infectious diseases and have shown recent potential to treat cancers through active immunotherapy. Soluble polysaccharides elicit short-lasting immune responses and are usually covalently linked to immunogenic carrier proteins to enhance the antigen-specific immune response by stimulating T-cell-dependent mechanisms. Nonetheless, the conjugation of purified polysaccharides to carrier proteins complexifies vaccine production, and immunization with protein glycoconjugates can lead to the undesirable immunogenic interference of the carrier.

Probing the molecular determinants of the activation of toll-like receptor 2/6 by amyloid nanostructures through directed peptide self-assembly.

Amyloid fibrils are proteinaceous nanostructures known for their ability to activate the innate immune system, which has been recently exploited for their use as self-adjuvanted antigen delivery systems for vaccines. Among mechanisms of immunostimulation, the activation of the heterodimeric toll-like receptor 2/6 (TLR2/TLR6) by the cross-β-sheet quaternary conformation appears important. Nonetheless, the lack of control over the process of self-assembly and the polydispersity of the resulting supramolecular architectures make it challenging to elucidate the molecular basis of TLR2/TLR6 engagement by amyloid assemblies.

Convergent Synthesis of a Group B Type III Epitope Toward a Semisynthetic Carbohydrate-Based Vaccine.

In this work, we synthesized an hexasaccharide derived from the capsular polysaccharide of group B type III capsular polysaccharide. Our convergent 3 + 3 strategy avoided the use of benzyl protecting groups allowing the installation of an azide anchoring group and providing a high yield for the final deprotection steps. Moreover, the minimal hexasaccharidic epitope was conjugated to CRM and BSA via copper-catalyzed azide-alkyne cycloaddition for the preparation of a semisynthetic carbohydrate-based vaccine.