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Archaeosome adjuvants: immunological capabilities and mechanism(s) of action.

机译:古细菌佐剂:免疫功能和作用机制。

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Archaeosomes (liposomes comprised of glycerolipids of Archaea) constitute potent adjuvants for the induction of Th1, Th2 and CD8(+) T cell responses to the entrapped soluble antigen. Archaeal lipids are uniquely constituted of ether-linked isoprenoid phytanyl cores conferring stability to the membranes. Additionally, varied head groups displayed on the glycerol-lipid cores facilitate unique immunostimulating interactions with mammalian antigen-presenting cells (APCs). The polar lipid from the archaeon, Methanobrevibacter smithii has been well characterized for its adjuvant potential, and is abundant in archaetidyl serine, promoting interaction with a phosphatidylserine receptor on APCs. These archaeosomes mediate MHC class I cross-priming via the phagosome-to-cytosol TAP-dependent classical processing pathway, and also upregulate costimulation by APCs without overt inflammatory cytokine production. Furthermore, they facilitate potent CD8(+) T cell memory to co-delivered antigen, comparable in magnitudeand quality to live bacterial vaccine vectors. Archaeosome vaccines provide profound protection in murine models of infection and cancer. This technology is being developed for clinical application and offers a novel prospect for rational design and development of safe and potent subunit vaccines capable of eliciting T cell immunity against intracellular infections and cancers.
机译:考古小体(由古细菌的甘油脂质组成的脂质体)构成有效的佐剂,可诱导Th1,Th2和CD8(+)T细胞对捕获的可溶性抗原的反应。初生脂质独特地由醚连接的类异戊二烯植烷酰基核构成,赋予膜以稳定性。另外,在甘油-脂质核心上展示的不同头基促进了与哺乳动物抗原呈递细胞(APC)的独特免疫刺激相互作用。来自古细菌的史密斯甲烷短杆菌属的极性脂质具有良好的佐剂潜能,并且在古生物基丝氨酸中含量丰富,可促进与APC上的磷脂酰丝氨酸受体的相互作用。这些古细菌通过吞噬体-细胞质TAP依赖的经典加工途径介导MHC I类交叉引发,并且在没有明显的炎症细胞因子产生的情况下,也上调了APC的共刺激作用。此外,它们还促进了有效的CD8(+)T细胞记忆以共同递送抗原,其强度和质量与活细菌疫苗载体相当。古细菌疫苗在鼠类感染和癌症模型中提供了深远的保护。这项技术正在为临床应用开发,为合理设计和开发能够引发针对细胞内感染和癌症的T细胞免疫力的安全有效的亚基疫苗提供了新的前景。

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