Meng Tianyao, James Brady, Haymore Jared, Wang Rui, Gubler Shawn, Taylor Seth A, Finn M G, Teyton Luc, Deng Shenglou, Savage Paul B
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
Tetrahedron. 2024 Sep 28;165. doi: 10.1016/j.tet.2024.134186. Epub 2024 Aug 8.
We developed a method for making immune responses to bacterial glycans T cell-dependent, which involves attachment of short, synthetic glycans to a virus-like nanoparticle (VLP). This strategy enhances immune responses to glycans by facilitating cognate T cell help of B cells, leading to antibody class switching and affinity maturation yielding high-affinity, anti-glycan antibodies. This method requires synthesis of bacterial glycans as propargyl glycosides for covalent attachment to VLPs, and the resulting short linker between the VLP and glycan is important for optimal T cell receptor recognition. In this work, glycans that are part of the capsular polysaccharides (CPS) produced by serotypes Sp6A and Sp6B were synthesized as disaccharides and trisaccharides. The optimal glycan epitope for antibody binding to the CPS from these serotypes is unknown, and differing "frames" of disaccharides and trisaccharides were prepared to elucidate the optimal antigen for antibody binding.
我们开发了一种使针对细菌聚糖的免疫反应依赖T细胞的方法，该方法涉及将短的合成聚糖连接到病毒样纳米颗粒（VLP）上。这种策略通过促进B细胞的同源T细胞辅助来增强对聚糖的免疫反应，导致抗体类别转换和亲和力成熟，从而产生高亲和力的抗聚糖抗体。该方法需要将细菌聚糖合成为炔丙基糖苷以共价连接到VLP上，并且VLP与聚糖之间形成的短连接子对于最佳T细胞受体识别很重要。在这项工作中，将血清型Sp6A和Sp6B产生的荚膜多糖（CPS）的组成部分聚糖合成为二糖和三糖。尚不清楚抗体与这些血清型的CPS结合的最佳聚糖表位，因此制备了不同“框架”的二糖和三糖以阐明抗体结合的最佳抗原。
