Center for Neuroscience and Cell Biology , University of Coimbra , 3004-517 Coimbra , Portugal.
Faculty of Pharmacy, Pólo das Ciências da Saúde Azinhaga de Santa Comba , University of Coimbra , 3000-548 Coimbra , Portugal.
Mol Pharm. 2019 May 6;16(5):1971-1981. doi: 10.1021/acs.molpharmaceut.8b01322. Epub 2019 Apr 23.
The lack of vaccine adjuvants that are able to induce robust T cell responses fosters the search for more powerful options. Pathogen-like particles are a promising approach. The adjuvant activity of pathogen-like particles is highly influenced by size and surface composition. This study aimed to evaluate the adjuvant potential of two different β-glucan-based particles, blend chitosan/β-glucan particles (ChiGluPs), which are positively charged and have mean size of 1276 nm, and neutral yeast-derived glucan particles (GPs), with a mean size of 3 μm. Additionally, chitosan particles (ChiPs) were used to understand the effect of β-glucan addition (ChiGluPs). Mouse spleen cells responded through the production of either TNF-α or RANTES, following in vitro stimulation with particles containing either β-glucan (ChiGluPs and GPs) or chitosan (ChiGluPs and ChiPs). Human monocytes responded to all particles through TNF-α secretion. Subcutaneous vaccination of mice with the hepatitis B surface antigen (HBsAg) showed increased serum IgG for all particles compared to HBsAg alone (435-, 4500-, or 2500-fold increase for either ChiPs, ChiGluPs, or GPs). Interestingly, only GPs elicited the secretion of HBsAg-specific Th1, Th2, Th9, Th17, Th22, and Treg-related cytokines. This study demonstrates, for the first time, that GPs can have a significant role against the hepatitis B virus by favoring antiviral immunity.
缺乏能够诱导强壮 T 细胞反应的疫苗佐剂,促使人们寻找更有效的选择。类病原体颗粒是一种很有前途的方法。类病原体颗粒的佐剂活性受大小和表面组成的强烈影响。本研究旨在评估两种不同的基于β-葡聚糖的颗粒的佐剂潜力,一种是带正电荷、平均粒径为 1276nm 的壳聚糖/β-葡聚糖颗粒(ChiGluPs),另一种是平均粒径为 3μm 的中性酵母衍生葡聚糖颗粒(GPs)。此外,还使用壳聚糖颗粒(ChiPs)来了解β-葡聚糖添加(ChiGluPs)的影响。小鼠脾细胞通过产生 TNF-α 或 RANTES 来响应,这是通过体外刺激含有β-葡聚糖(ChiGluPs 和 GPs)或壳聚糖(ChiGluPs 和 ChiPs)的颗粒而产生的。所有颗粒都能通过 TNF-α 分泌刺激人单核细胞。用乙型肝炎表面抗原(HBsAg)对小鼠进行皮下接种,与单独使用 HBsAg 相比,所有颗粒的血清 IgG 都增加了(ChiPs、ChiGluPs 或 GPs 的增加分别为 435-、4500-或 2500 倍)。有趣的是,只有 GPs 能诱导 HBsAg 特异性 Th1、Th2、Th9、Th17、Th22 和 Treg 相关细胞因子的分泌。本研究首次证明,GPs 通过促进抗病毒免疫,在对抗乙型肝炎病毒方面可以发挥重要作用。