Wang Zhen, Enotarpi Jacopo, Buffi Giada, Pezzicoli Alfredo, Gstöttner Christoph J, Nicolardi Simone, Balducci Evita, Fabbrini Monica, Romano Maria Rosaria, van der Marel Gijsbert A, Del Bino Linda, Adamo Roberto, Codée Jeroen D C
Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
GSK Siena Italy, Via Fiorentina 1 Siena 53100, Italy.
JACS Au. 2022 Jul 6;2(7):1724-1735. doi: 10.1021/jacsau.2c00302. eCollection 2022 Jul 25.
Group B (GBS) is a Gram-positive bacterium and the most common cause of neonatal blood and brain infections. At least 10 different serotypes exist, that are characterized by their different capsular polysaccharides. The Group B carbohydrate (GBC) is shared by all serotypes and therefore attractive be used in a glycoconjugate vaccine. The GBC is a highly complex multiantennary structure, composed of rhamnose rich oligosaccharides interspaced with glucitol phosphates. We here report the development of a convergent approach to assemble a pentamer, octamer, and tridecamer fragment of the termini of the antennae. Phosphoramidite chemistry was used to fuse the pentamer and octamer fragments to deliver the 13-mer GBC oligosaccharide. Nuclear magnetic resonance spectroscopy of the generated fragments confirmed the structures of the naturally occurring polysaccharide. The fragments were used to generate model glycoconjugate vaccine by coupling with CRM197. Immunization of mice delivered sera that was shown to be capable of recognizing different GBS strains. The antibodies raised using the 13-mer conjugate were shown to recognize the bacteria best and the serum raised against this GBC fragment-mediated opsonophagocytic killing best, but in a capsule dependent manner. Overall, the GBC 13-mer was identified to be a highly promising antigen for incorporation into future (multicomponent) anti-GBS vaccines.
B组链球菌（GBS）是一种革兰氏阳性细菌，是新生儿血液和脑部感染的最常见病因。至少存在10种不同的血清型，其特征在于它们不同的荚膜多糖。B组碳水化合物（GBC）为所有血清型所共有，因此有望用于糖缀合物疫苗。GBC是一种高度复杂的多天线结构，由富含鼠李糖的寡糖与葡糖醇磷酸酯相间排列组成。我们在此报告了一种用于组装触角末端五聚体、八聚体和十三聚体片段的汇聚方法。使用亚磷酰胺化学方法将五聚体和八聚体片段融合，以得到13聚体的GBC寡糖。对所生成片段进行核磁共振光谱分析，证实了天然存在的多糖的结构。通过与CRM197偶联，这些片段被用于生成模型糖缀合物疫苗。对小鼠进行免疫接种后获得的血清能够识别不同的GBS菌株。结果表明，使用13聚体缀合物产生的抗体对细菌的识别能力最强，针对该GBC片段产生的血清介导的调理吞噬杀伤作用最佳，但具有荚膜依赖性。总体而言，GBC 13聚体被确定为一种非常有前景的抗原，可纳入未来的（多组分）抗GBS疫苗中。
