GSK, Via Fiorentina 1, 53100 Siena, Italy.
Chem Soc Rev. 2018 Dec 10;47(24):9015-9025. doi: 10.1039/c8cs00495a.
Glycoconjugate vaccines obtained by chemical linkage of a carbohydrate antigen to a protein are part of routine vaccinations in many countries. Licensed antimicrobial glycan-protein conjugate vaccines are obtained by random conjugation of native or sized polysaccharides to lysine, aspartic or glutamic amino acid residues that are generally abundantly exposed on the protein surface. In the last few years, the structural approaches for the definition of the polysaccharide portion (epitope) responsible for the immunological activity has shown potential to aid a deeper understanding of the mode of action of glycoconjugates and to lead to the rational design of more efficacious and safer vaccines. The combination of technologies to obtain more defined carbohydrate antigens of higher purity and novel approaches for protein modification has a fundamental role. In particular, methods for site selective glycoconjugation like chemical or enzymatic modification of specific amino acid residues, incorporation of unnatural amino acids and glycoengineering, are rapidly evolving. Here we discuss the state of the art of protein engineering with carbohydrates to obtain glycococonjugates vaccines and future perspectives.
糖缀合物疫苗是通过将碳水化合物抗原与蛋白质化学连接而获得的，它们是许多国家常规疫苗接种的一部分。经过许可的抗菌聚糖-蛋白缀合物疫苗是通过将天然或大小合适的多糖随机缀合到赖氨酸、天冬氨酸或谷氨酸氨基酸残基上而获得的，这些残基通常在蛋白质表面大量暴露。在过去的几年中，用于定义负责免疫活性的多糖部分（表位）的结构方法显示出有助于更深入了解糖缀合物作用模式并导致更有效和更安全疫苗的合理设计的潜力。获得更高纯度的更明确的碳水化合物抗原的技术组合和用于蛋白质修饰的新方法起着至关重要的作用。特别是，用于糖基化的化学或酶修饰、非天然氨基酸的掺入和糖工程化等用于选择性糖基化的方法正在迅速发展。在这里，我们讨论了用碳水化合物获得糖缀合物疫苗的蛋白质工程的最新技术和未来展望。
