Recent Advances in Toll Like Receptor-Targeting Glycoconjugate Vaccines

Many malignant cell surface carbohydrates resulting from abnormal glycosylation patterns of certain diseases can serve as antigens for the development of vaccines against these diseases. However, carbohydrate antigens are usually poorly immunogenic by themselves, thus they need to be covalently coupled with immunologically active carrier molecules to be functional. The most well established and commonly used carriers are proteins. In recent years, the use of toll-like receptor (TLR) ligands to formulate glycoconjugate vaccines has gained significant attention because TLR ligands can serve not only as carrier molecules but also as built-in adjuvants to form fully synthetic and self-adjuvanting conjugate vaccines, which have several advantages over carbohydrate-protein conjugates and formulated mixtures with external adjuvants. This article reviews recent progresses in the development of conjugate vaccines based on TLR ligands. Two major classes of TLR ligands, lipopeptides and lipid A derivatives will be covered with more focus on monophosohoryl lipid A (MPLA) and related analogs, which are TLR4 ligands demonstrated to be able to provoke T cell-dependent, adaptive immune responses. Corresponding conjugate vaccines have shown promising application potentials to multiple diseases including cancer.