Bio-Organic Chemistry Unit, CNR- Institute of Biomolecular Chemistry, Via Campi Flegrei 34, IT-80078, Pozzuoli, Napoli, Italy.
University of Campania, Clinical Immunology and Allergology, Dept. of Internal and Experimental Clinic, c/o II Policlinico (Bd. 3), Via S. Pansini, 5, 80131, Napoli, Italy.
Sci Rep. 2017 Jul 24;7(1):6286. doi: 10.1038/s41598-017-05969-8.
Dendritic Cells (DCs) recognize infectious non-self molecules and engage the adaptive immune system thereby initiating long lasting, antigen-specific responses. As such, the ability to activate DCs is considered a key tool to enhance the efficacy and quality of vaccination. Here we report a novel immunomodulatory sulfolipid named β-SQDG18 that prototypes a class of natural-derived glycolipids able to prime human DCs by a TLR2/TLR4-independent mechanism and trigger an efficient immune response in vivo. β-SQDG18 induces maturation of DC with the upregulation of MHC II molecules and co-stimulatory proteins (CD83, CD86), as well as pro-inflammatory cytokines (IL-12 and INF-γ). Mice immunized with OVA associated to β-SQDG18 (1:500) produced a titer of anti-OVA Ig comparable to traditional adjuvants. In an experimental model of melanoma, vaccination of C57BL/6 mice with β-SQDG18-adjuvanted hgp10 peptide elicited a protective response with a reduction in tumour growth and increase in survival.
树突状细胞(DCs)识别感染性非自身分子,并激活适应性免疫系统,从而引发持久的、抗原特异性的反应。因此,激活 DCs 的能力被认为是增强疫苗效力和质量的关键工具。在这里,我们报告了一种新型免疫调节硫酸鞘糖脂β-SQDG18,它是一类天然衍生糖脂的原型,可以通过 TLR2/TLR4 非依赖机制激活人 DCs,并在体内引发有效的免疫反应。β-SQDG18 通过上调 MHC II 分子和共刺激蛋白(CD83、CD86)以及促炎细胞因子(IL-12 和 INF-γ)来诱导 DC 的成熟。用与β-SQDG18(1:500)偶联的 OVA 免疫小鼠可产生与传统佐剂相当的抗 OVA Ig 滴度。在黑色素瘤的实验模型中,用β-SQDG18 佐剂的 hgp10 肽对 C57BL/6 小鼠进行疫苗接种可引发保护性反应,肿瘤生长减少,存活率提高。