Recent Advances in Toll Like Receptor-Targeting Glycoconjugate Vaccines.
Recent Advances in Toll Like Receptor-Targeting Glycoconjugate Vaccines.
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DOI：
10.3390/molecules23071583
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发表时间：
2018-06-29
期刊：
影响因子：
--
通讯作者：
Guo Z
中科院分区：
文献类型：
--
作者：
Li Q;Guo Z
由于某些疾病的糖基化模式异常而产生的许多恶性细胞表面碳水化合物可以作为抗原，用于开发针对这些疾病的疫苗。然而，碳水化合物抗原本身的免疫原性通常很差，因此它们需要与具有免疫活性的载体分子共价偶联才能发挥作用。最成熟和最常用的载体是蛋白质。近年来，利用Toll样受体(Toll-like Receptor，TLR)配体制备糖结合疫苗引起了人们的广泛关注，因为TLR配体不仅可以作为载体分子，还可以作为内置佐剂形成完全合成的、自佐剂的结合疫苗，与碳水化合物-蛋白质结合物和与外部佐剂的配方混合物相比具有一些优点。本文综述了基于TLR配体的结合疫苗的研究进展。两类主要的TLR配体，脂肽和类脂A衍生物将更多地关注单磷酰脂A及其类似物，这些TLR4配体被证明能够激发T细胞依赖的获得性免疫反应。相应的结合疫苗在包括癌症在内的多种疾病中显示出良好的应用前景。
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.
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