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

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.

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Fig. 1: GFPBW1 promotes the maturation and activation of APCs in vitro.
Fig. 2: GFPBW1 enhances OVA antigen-specific immune responses.
Fig. 3: GFPBW1 has well immunologic tolerance and safety.
Fig. 4: GFPBW1 can replenish aluminum adjuvant-deficient Th1-type immune response.
Fig. 5: GFPBW1 exerts potent antitumour efficacy in a preventive tumor vaccine model.
Fig. 6: GFPBW1 exerts potent antitumour efficacy in a therapeutic tumor vaccine model.
Fig. 7: GFPBW1 promotes the expression of genes associated with humoral and cellular immunity in tumor tissues.

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Data availability

All data are available in the main text, the Supporting Information materials, or upon request from the corresponding author. Correspondence and requests for materials should be addressed to YFY, LKG, JHS, and KD.

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Acknowledgements

This work is supported by the National Natural Science Foundation of China (82341039), the National Key Research and Development Plan (2022YFC2304105), Shanghai Municipal Science and Technology Major Project, the Science and Technology Innovation Action Plan of Shanghai (22S11902100, 22140900500), and the National Science Foundation for Distinguished Young Scholars of China (32271332). This work was also partial supported by the Zhongshan Municipal Bureau of Science and Technology (CXTD2023010) and Department of Science and Technology of Guangdong Province (High-level Innovative Research Institute 2021B0909050003). We would like to thank colleagues from the Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, and Shanghai Institute of Materia Medica, Chinese Academy of Sciences, who provided advice and technical support, thanks for the support of Anling Biomed (SuZhou) Co., Ltd for the animal experiment.

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YFY, LKG, JHS, KD, XH, YRL, WFL and JLL designed the experiments and analyzed the data. XH, JLL, and YRL performed the experiments and prepared the paper. XZ, QZ, WFL, HLL and GYH assisted in performing the experiments. All authors approved the final draft of the paper.

Corresponding authors

Correspondence to Kan Ding, Jian-hua Sun, Li-kun Gong or Yi-fu Yang.

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He, X., Lu, Jl., Liao, Wf. et al. GFPBW1, a β-glucan from Grifola frondosa as vaccine adjuvant: APCs activation and maturation. Acta Pharmacol Sin (2024). https://doi.org/10.1038/s41401-024-01330-8

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