作为疫苗佐剂的 GFPBW1--一种来自蕨类植物的β-葡聚糖:APCs 的激活和成熟

IF 6.9 1区 医学 Q1 CHEMISTRY, MULTIDISCIPLINARY Acta Pharmacologica Sinica Pub Date : 2024-11-01 Epub Date: 2024-06-21 DOI:10.1038/s41401-024-01330-8
Xiang He, Jiang-Ling Lu, Wen-Feng Liao, Yi-Ru Long, Xing Zhang, Qian Zhu, Heng-Lei Lu, Geng-Yan Hao, Kan Ding, Jian-Hua Sun, Li-Kun Gong, Yi-Fu Yang
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引用次数: 0

摘要

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,我们从果粒花生(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。本研究利用 OVA 抗原和 B16-OVA 肿瘤模型探讨了 GFPBW1 的辅助作用。我们发现,GFPBW1(5、50、500 μg/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。我们用 OVA 与 GFPBW1(50 或 300 μg)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与铝联合使用可显著提高OVA特异性IgG2a和IgG2b的滴度,但不能提高IgG1的滴度,这表明GFPBW1可作为铝的辅助佐剂来弥补Th1的不足。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 DCs、B1 细胞和浆细胞增加,这与其激活和成熟 APCs 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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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.

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来源期刊
Acta Pharmacologica Sinica
Acta Pharmacologica Sinica 医学-化学综合
CiteScore
15.10
自引率
2.40%
发文量
4365
审稿时长
2 months
期刊介绍: APS (Acta Pharmacologica Sinica) welcomes submissions from diverse areas of pharmacology and the life sciences. While we encourage contributions across a broad spectrum, topics of particular interest include, but are not limited to: anticancer pharmacology, cardiovascular and pulmonary pharmacology, clinical pharmacology, drug discovery, gastrointestinal and hepatic pharmacology, genitourinary, renal, and endocrine pharmacology, immunopharmacology and inflammation, molecular and cellular pharmacology, neuropharmacology, pharmaceutics, and pharmacokinetics. Join us in sharing your research and insights in pharmacology and the life sciences.
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