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Glycan Array Evaluation of Synthetic Epitopes between the Capsular Polysaccharides from Streptococcus pneumoniae 19F and 19A
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2021-09-01 , DOI: 10.1021/acschembio.1c00347
Laura Morelli 1 , Luigi Lay 2 , Darielys Santana-Mederos 3 , Yury Valdes-Balbin 3 , Vicente Verez Bencomo 3 , Angela van Diepen 4 , Cornelis H Hokke 4 , Fabrizio Chiodo 4, 5 , Federica Compostella 1
Affiliation  

Vaccination represents the most effective way to prevent invasive pneumococcal diseases. The glycoconjugate vaccines licensed so far are obtained from capsular polysaccharides (CPSs) of the most virulent serotypes. Protection is largely limited to the specific vaccine serotypes, and the continuous need for broader coverage to control the outbreak of emerging serotypes is pushing the development of new vaccine candidates. Indeed, the development of efficacious vaccine formulation is complicated by the high number of bacterial serotypes with different CPSs. In this context, to simplify vaccine composition, we propose the design of new saccharide fragments containing chemical structures shared by different serotypes as cross-reactive and potentially cross-protective common antigens. In particular, we focused on Streptococcus pneumoniae (Sp) 19A and 19F. The CPS repeating units of Sp 19F and 19A are very similar and share a common structure, the disaccharide ManNAc-β-(1→4)-Glc (A-B). Herein, we describe the synthesis of a small library of compounds containing different combinations of the common 19F/19A disaccharide. The six new compounds were tested with a glycan array to evaluate their recognition by antibodies in reference group 19 antisera and factor reference antisera (reacting against 19F or 19A). The disaccharide A-B, phosphorylated at the upstream end, emerged as a hit from the glycan array screening because it is strongly recognized by the group 19 antisera and by the 19F and 19A factor antisera, with similar intensity compared with the CPSs used as controls. Our data give a strong indication that the phosphorylated disaccharide A-B can be considered a common epitope among different Sp 19 serotypes.

中文翻译:

肺炎链球菌 19F 和 19A 荚膜多糖间合成表位的聚糖阵列评估

接种疫苗是预防侵袭性肺炎球菌疾病的最有效方法。迄今为止获得许可的糖缀合物疫苗是从毒性最强的血清型的荚膜多糖 (CPS) 中获得的。保护在很大程度上仅限于特定的疫苗血清型,并且不断需要更广泛的覆盖范围来控制新兴血清型的爆发,这正在推动新候选疫苗的开发。事实上,由于具有不同 CPS 的大量细菌血清型,有效疫苗制剂的开发变得复杂。在这种情况下,为了简化疫苗组成,我们建议设计包含不同血清型共享的化学结构的新糖片段,作为交叉反应和潜在的交叉保护共同抗原。特别是,我们专注于肺炎链球菌(Sp) 19A 和 19F。Sp 19F 和 19A 的 CPS 重复单元非常相似,具有共同的结构,即双糖 ManNAc-β-(1→4)-Glc (AB)。在此,我们描述了包含常见 19F/19A 二糖的不同组合的小型化合物库的合成。用聚糖阵列测试了六种新化合物,以评估它们被参考组 19 抗血清和因子参考抗血清(针对 19F 或 19A 反应)中的抗体识别。在上游末端磷酸化的二糖 AB 出现在聚糖阵列筛选中,因为它被组 19 抗血清以及 19F 和 19A 因子抗血清强烈识别,与用作对照的 CPS 相比强度相似。
更新日期:2021-09-17
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