上海中医药大学杨以阜等研究人员合作发现， 一种来自贝叶奇果菌的β-葡聚糖GFPBW1可作为疫苗佐剂。相关论文于2024年6月21日在线发表于国际学术期刊《中国药理学报》。

研究人员表示，目前还缺乏具有改善适应性免疫（尤其是通过抗原呈递细胞（APC）的杠杆作用）特性的疫苗佐剂。在之前的研究中，研究人员从贝叶奇果菌（Granola frondosa）的果实体内获得了一种名为GFPBW1的新型可溶性300 kDa均质β-葡聚糖。GFPBW1可通过靶向树突状细胞相关C型凝集素1（Dectin-1）/Syk/NF-κB信号激活巨噬细胞，从而达到抗肿瘤的效果。

研究人员利用OVA抗原和B16-OVA肿瘤模型探讨了GFPBW1的佐剂作用。研究人员发现，GFPBW1（5、50、500μg/mL）可通过增加CD80、CD86和MHC II的表达，剂量依赖性地促进体外APC的活化和成熟。研究人员用OVA与GFPBW1（50或300μg）联合免疫雌性小鼠两次，每次间隔两周。GFPBW1能明显增加不同亚型的OVA特异性抗体滴度，包括IgG1、IgG2a、IgG2b和IgG3，这表明它可以作为Th1和Th2型免疫反应的佐剂。

此外，GFPBW1与铝联合使用能显著提高OVA特异性IgG2a和IgG2b的滴度，但不能提高IgG1的滴度。用OVA加GFPBW1免疫的小鼠，其主要器官和注射部位均未发现明显的病理损伤，血液学指标也未发现异常。GFPBW1作为B16-OVA癌症疫苗模型的佐剂，在预防性疫苗中可实现对肿瘤的全面抑制，在治疗性疫苗中可提高抗肿瘤效果。

研究人员发现，差异表达基因富集于抗原处理过程中，特别是在OVA加GFPBW1组中，肿瘤浸润的DC、B1细胞和浆细胞增加，这与其激活和成熟APC的功能相符。总之，这项研究系统地描述了GFPBW1作为一种新型强效安全佐剂的特性，并强调了它在疫苗开发中的巨大潜力。

附：英文原文

Title: GFPBW1, a β-glucan from Grifola frondosa as vaccine adjuvant: APCs activation and maturation

Author: He, Xiang, Lu, Jiang-ling, Liao, Wen-feng, Long, Yi-ru, Zhang, Xing, Zhu, Qian, Lu, Heng-lei, Hao, Geng-yan, Ding, Kan, Sun, Jian-hua, Gong, Li-kun, Yang, Yi-fu

Issue&Volume: 2024-06-21

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 300kDa 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, 500μg/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 300μg) 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.

DOI: 10.1038/s41401-024-01330-8

Source: https://www.nature.com/articles/s41401-024-01330-8