Figure 2. Schematic representation of glycoconjugate immunogen design.

Starting from activated glycans (* denotes activated group) from natural or synthetic sources, the production of three categories of glycoconjugate immunogens are shown: protein conjugates, lipid conjugates and polyvalent scaffold conjugates. The requirement for both polyvalent display and T helper epitopes, critical for achieving strong, long-lasting and class-switched Ab responses, are satisfied in each category. For protein conjugates, activated glycans are covalently attached to immunogenic protein carriers (e.g. KLH), which provide T helper epitopes and enable polyvalent display. Lipid conjugates, made by covalent linkage of activated glycans to T helper peptides attached to lipid moieties, allow polyvalency through formulation into lipid membranes. In addition, activated glycans may first be conjugated to synthetic polyvalent scaffolds (e.g. dendron, MAG and RAFT) which may then be used to make protein and lipid conjugates. Alternatively, polyvalent scaffold conjugates may be made through addition of T helper peptides alone. Adjuvants are usually included in the final glycoconjugate vaccine formulations (e.g. Alum and QS-21). Note: Pam₃Cys also has adjuvant properties. MAG: multiple antigen glycopeptides. RAFT: regioselectively addressable functionalized templates