Abstract：
Adjuvants for vaccines with characteristics of improving adaptive immunity particularly via leverage of antigen presenting cells (APCs) are currently lacking. In a previous work we obtained a new soluble 300 kDa homogeneous β-glucan named GFPBW1 from the fruit bodies of Granola frondosa. GFPBW1 could activate macrophages by targeting dendritic cell associated C-type lectin 1 (Dectin-1)/Syk/NF-κB signaling to achieve antitumour effects. In this study the adjuvant effects of GFPBW1 were explored with OVA-antigen and B16-OVA tumor model. We showed that GFPBW1 (5, 50, 500 μg/mL) dose-dependently promoted activation and maturation of APCs in vitro by increasing CD80, CD86 and MHC II expression. We immunized female mice with OVA in combination with GFPBW1 (50 or 300 μg) twice with an interval of two weeks. GFPBW1 markedly and dose-dependently increased OVA-specific antibody titers of different subtypes including IgG1, IgG2a, IgG2b and IgG3, suggesting that it could serve as an adjuvant for both Th1 and Th2 type immune responses. Furthermore, GFPBW1 in combination with aluminum significantly increased the titers of OVA-specific IgG2a and IgG2b, but not those of IgG1, suggesting that GFPBW1 could be used as a co-adjuvant of aluminum to compensate for Th1 deficiency. For mice immunized with OVA plus GFPBW1, no obvious pathological injury was observed in either major organs or injection sites, and no abnormalities were noted for any of the hematological parameters. When GFPBW1 served as an adjuvant in the B16-OVA cancer vaccine models, it could accomplish entire tumor suppression with preventive vaccines, and enhance antitumour efficacy with therapeutic vaccines. Differentially expressed genes were found to be enriched in antigen processing process, specifically increased tumor infiltration of DCs, B1 cells and plasma cells in the OVA plus GFPBW1 group, in accordance with its activation and maturation function of APCs. Collectively, this study systematically describes the properties of GFPBW1 as a novel potent and safe adjuvant and highlights its great potential in vaccine development.
摘要：
目前缺乏具有特别是通过利用抗原呈递细胞(APC)改善适应性免疫的特征的疫苗佐剂。在先前的工作中，我们从Granolafrondosa的子实体中获得了一种新的可溶性300kDa均质β-葡聚糖，名为GFPBW1。GFPBW1可以通过靶向树突状细胞相关的C型凝集素1（Dectin-1）/Syk/NF-κB信号来激活巨噬细胞，从而实现抗肿瘤作用。在这项研究中，用OVA抗原和B16-OVA肿瘤模型探索了GFPBW1的佐剂作用。我们表明，GFPBW1（5、50、500μg/mL）通过增加CD80，CD86和MHCII表达而剂量依赖性地促进APC的体外激活和成熟。我们用OVA与GFPBW1(50或300μg)组合免疫雌性小鼠两次,间隔两周。GFPBW1显着和剂量依赖性地增加不同亚型的OVA特异性抗体滴度，包括IgG1，IgG2a，IgG2b和IgG3，表明它可以作为Th1和Th2型免疫应答的佐剂。此外，GFPBW1与铝组合显着增加OVA特异性IgG2a和IgG2b的滴度，而不是IgG1，这表明GFPBW1可以用作铝的辅助佐剂来补偿Th1缺乏。对于用OVA加GFPBW1免疫的小鼠，在主要器官或注射部位均未观察到明显的病理损伤。并且没有注意到任何血液学参数的异常。当GFPBW1在B16-OVA癌症疫苗模型中作为佐剂时，它可以用预防性疫苗完成整个肿瘤抑制，用治疗性疫苗增强抗肿瘤功效。发现差异表达基因在抗原加工过程中富集，特异性增加的DC肿瘤浸润，OVA加GFPBW1组的B1细胞和浆细胞，根据其对APC的激活和成熟功能。总的来说，这项研究系统地描述了GFPBW1作为一种新型有效和安全的佐剂的特性，并强调了其在疫苗开发中的巨大潜力。
