State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, PR China.
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, College of Chemistry, Central China Normal University, Wuhan, Hubei, 430079, PR China.
Carbohydr Res. 2022 Mar;513:108527. doi: 10.1016/j.carres.2022.108527. Epub 2022 Feb 23.
iNKT cells are a special type of T cell that acts as a link between the innate and adaptive immune systems, with the capacity to stimulate a wide range of cell types. The glycolipid α-galactosylceramide (αGC) is a robust agonist of iNKT cells and induces the secretion of Th1- and Th2-type cytokines. αGC and its analogs are widely used as adjuvants to enhance immune responses against viral, parasitic, and bacterial pathogens. This review first discusses the challenges of using free αGC as a vaccine adjuvant to treat infectious diseases. We next present strategies to realize the potential of the adjuvant effect of iNKT cell glycolipids, including (1) the use of Th1- or Th2-biasing αGC analogs, (2) covalent conjugation of glycolipid with antigen, (3) particulate vehicle-assisted delivery of glycolipid, (4) glycolipid-loaded cellular systems, (5) glycolipid combination with other immunostimulants, and (6) usage as mucosal adjuvants. Finally, we discuss future approaches for the development of iNKT cell agonists used as vaccine adjuvants against infectious diseases.
iNKT 细胞是一种特殊类型的 T 细胞，充当先天免疫和适应性免疫系统之间的桥梁，具有刺激多种细胞类型的能力。糖脂 α-半乳糖基神经酰胺（αGC）是 iNKT 细胞的有效激动剂，可诱导 Th1 和 Th2 型细胞因子的分泌。αGC 及其类似物被广泛用作佐剂，以增强针对病毒、寄生虫和细菌病原体的免疫反应。本综述首先讨论了使用游离 αGC 作为疫苗佐剂治疗传染病的挑战。接下来，我们提出了实现 iNKT 细胞糖脂佐剂作用潜力的策略，包括（1）使用偏向 Th1 或 Th2 的 αGC 类似物，（2）糖脂与抗原的共价偶联，（3）颗粒载体辅助糖脂递送，（4）负载糖脂的细胞系统，（5）糖脂与其他免疫刺激剂联合使用，以及（6）作为黏膜佐剂的使用。最后，我们讨论了开发用作传染病疫苗佐剂的 iNKT 细胞激动剂的未来方法。
