Anish Chakkumkal, Beurret Michel, Poolman Jan
Bacterial Vaccines Discovery and Early Development, Janssen Vaccines and Prevention B.V., Leiden, Netherlands.
NPJ Vaccines. 2021 Dec 10;6(1):150. doi: 10.1038/s41541-021-00409-1.
The development and use of antibacterial glycoconjugate vaccines have significantly reduced the occurrence of potentially fatal childhood and adult diseases such as bacteremia, bacterial meningitis, and pneumonia. In these vaccines, the covalent linkage of bacterial glycans to carrier proteins augments the immunogenicity of saccharide antigens by triggering T cell-dependent B cell responses, leading to high-affinity antibodies and durable protection. Licensed glycoconjugate vaccines either contain long-chain bacterial polysaccharides, medium-sized oligosaccharides, or short synthetic glycans. Here, we discuss factors that affect the glycan chain length in vaccines and review the available literature discussing the impact of glycan chain length on vaccine efficacy. Furthermore, we evaluate the available clinical data on licensed glycoconjugate vaccine preparations with varying chain lengths against two bacterial pathogens, Haemophilus influenzae type b and Neisseria meningitidis group C, regarding a possible correlation of glycan chain length with their efficacy. We find that long-chain glycans cross-linked to carrier proteins and medium-sized oligosaccharides end-linked to carriers both achieve high immunogenicity and efficacy. However, end-linked glycoconjugates that contain long untethered stretches of native glycan chains may induce hyporesponsiveness by T cell-independent activation of B cells, while cross-linked medium-sized oligosaccharides may suffer from suboptimal saccharide epitope accessibility.
抗菌糖结合疫苗的研发与使用显著降低了儿童和成人潜在致命疾病的发生率，如菌血症、细菌性脑膜炎和肺炎。在这些疫苗中，细菌聚糖与载体蛋白的共价连接通过触发T细胞依赖性B细胞反应增强了糖类抗原的免疫原性，从而产生高亲和力抗体并提供持久保护。已获许可的糖结合疫苗要么含有长链细菌多糖、中等大小的寡糖，要么含有短的合成聚糖。在此，我们讨论影响疫苗中聚糖链长度的因素，并回顾现有文献中关于聚糖链长度对疫苗效力影响的讨论。此外，我们评估了针对两种细菌病原体——b型流感嗜血杆菌和C群脑膜炎奈瑟菌——具有不同链长的已获许可糖结合疫苗制剂的现有临床数据，以探讨聚糖链长度与其效力之间可能存在的相关性。我们发现，与载体蛋白交联的长链聚糖和与载体末端连接的中等大小寡糖均能实现高免疫原性和效力。然而，含有长段未连接天然聚糖链的末端连接糖结合物可能通过B细胞的非T细胞依赖性激活诱导低反应性，而交联的中等大小寡糖可能存在糖类表位可及性欠佳的问题。
