Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

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

Acta Pharmacologica Sinica volume 45, pages 2394–2404 (2024)Cite this article

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.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

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.

References

  1. Saxena M, van der Burg SH, Melief CJM, Bhardwaj N. Therapeutic cancer vaccines. Nat Rev Cancer. 2021;21:360–78.

    Article  PubMed  CAS  Google Scholar 

  2. Lin MJ, Svensson-Arvelund J, Lubitz GS, Marabelle A, Melero I, Brown BD, et al. Cancer vaccines: the next immunotherapy frontier. Nat Cancer. 2022;3:911–26.

    Article  PubMed  CAS  Google Scholar 

  3. Qi F, Zhao L, Zhou A, Zhang B, Li A, Wang Z, et al. The advantages of using traditional Chinese medicine as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer. Biosci Trends. 2015;9:16–34.

    Article  PubMed  CAS  Google Scholar 

  4. Zhang Y, Gu P, Wusiman A, Xu S, Ni H, Qiu T, et al. The immunoenhancement effects of polyethylenimine-modified Chinese Yam polysaccharide-encapsulated PLGA nanoparticles as an adjuvant. Int J Nanomed. 2020;15:5527–43.

    Article  CAS  Google Scholar 

  5. Wang QJ, Meng XY, Zhu L, Xu YL, Cui WP, He XH, et al. A polysaccharide found in flowers can enhance cellular and humoral immunity in chickens. Int J Biol Macromol. 2019;130:213–9.

    Article  PubMed  CAS  Google Scholar 

  6. Wang YQ, Mao JB, Zhou MQ, Jin YW, Lou CH, Dong Y, et al. Polysaccharide from activates TLR4-mediated signaling pathways in macrophages and shows immune adjuvant activity in mice. Int J Biol Macromol. 2019;123:157–66.

    Article  PubMed  CAS  Google Scholar 

  7. Feng HB, Fan J, Song ZH, Du XG, Chen Y, Wang JS, et al. Characterization and immunoenhancement activities of polysaccharides. Carbohydr Polym. 2016;136:803–11.

    Article  PubMed  CAS  Google Scholar 

  8. Hwang SH, Shin MS, Yoon TJ, Shin KS. Immunoadjuvant activity in mice of polysaccharides isolated from the leaves of CA Meyer. Int J Biol Macromol. 2018;107:2695–700.

    Article  PubMed  CAS  Google Scholar 

  9. Liu X, Chen S, Liu H, Xie J, Hasan KMF, Zeng Q, et al. Structural properties and anti-inflammatory activity of purified polysaccharides from Hen-of-the-woods mushrooms (Grifola frondosa). Front Nutr. 2023;10:1078868.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Fang J, Wang Y, Lv X, Shen X, Ni X, Ding K. Structure of a β-glucan from Grifola frondosa and its antitumor effect by activating Dectin-1/Syk/NF-κB signaling. Glycoconj J. 2012;29:365–77.

    Article  PubMed  CAS  Google Scholar 

  11. Taylor PR, Tsoni SV, Willment JA, Dennehy KM, Rosas M, Findon H, et al. Dectin-1 is required for β-glucan recognition and control of fungal infection. Nat Immunol. 2007;8:31–8.

    Article  PubMed  CAS  Google Scholar 

  12. Brown GD, Taylor PR, Reid DM, Willment JA, Williams DL, Martinez-Pomares L, et al. Dectin-1 is a major beta-glucan receptor on macrophages. J Exp Med. 2002;196:407–12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Mata-Martínez P, Bergón-Gutiérrez M, del Fresno C. Dectin-1 signaling update: new perspectives for trained immunity. Front Immunol. 2022;13:812148.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Carvalho A, Giovannini G, De Luca A, D’Angelo C, Casagrande A, Iannitti RG, et al. Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis. Cell Mol Immunol. 2012;9:276–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Leibundgut-Landmann S, Osorio F, Brown GD, Reis e Sousa C. Stimulation of dendritic cells via the dectin-1/Syk pathway allows priming of cytotoxic T-cell responses. Blood. 2008;112:4971–80.

    Article  PubMed  CAS  Google Scholar 

  16. Yu X, Long Y, Chen B, Tong Y, Shan M, Jia X, et al. PD-L1/TLR7 dual-targeting nanobody-drug conjugate mediates potent tumor regression via elevating tumor immunogenicity in a host-expressed PD-L1 bias-dependent way. J Immunother Cancer. 2022;10:e004590.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sun B, Yu S, Zhao D, Guo S, Wang X, Zhao K. Polysaccharides as vaccine adjuvants. Vaccine. 2018;36:5226–34.

    Article  PubMed  CAS  Google Scholar 

  18. Abbas AK, Murphy KM, Sher A. Functional diversity of helper T lymphocytes. Nature. 1996;383:787–93.

    Article  CAS  Google Scholar 

  19. Romagnani S. Th1/Th2 cells. Inflamm Bowel Dis. 1999;5:285–94.

    Article  PubMed  CAS  Google Scholar 

  20. Wan X, Yin Y, Zhou C, Hou L, Cui Q, Zhang X, et al. Polysaccharides derived from Chinese medicinal herbs: A promising choice of vaccine adjuvants. Carbohydr Polym. 2022;276:118739.

    Article  PubMed  CAS  Google Scholar 

  21. Hogenesch H. Mechanism of immunopotentiation and safety of aluminum adjuvants. Front Immunol. 2012;3:406.

    PubMed  Google Scholar 

  22. Zhang J, Chen Y, Zhang J, Wang Y, Liu Y. The Regulation of micro-organisms’ extra-cellular polysaccharides on immunity: a meta-analysis. Foods. 2022;11:1949.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Yang K, Chen J, Chen J, Wang Z, Song B, Li R, et al. The effect mechanism of polysaccharides inhibit tumor immune escape: A review. J Funct Foods. 2023;107:105638.

    Article  CAS  Google Scholar 

  24. Kikete S, Luo L, Jia B, Wang L, Ondieki G, Bian Y. Plant-derived polysaccharides activate dendritic cell-based anti-cancer immunity. Cytotechnology. 2018;70:1097–110.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Zhang W, Zheng X, Cheng N, Gai W, Xue X, Wang Y, et al. Isatis indigotica root polysaccharides as adjuvants for an inactivated rabies virus vaccine. Int J Biol Macromolecules. 2016;87:7–15.

    Article  CAS  Google Scholar 

  26. Broaders KE, Cohen JA, Beaudette TT, Bachelder EM, Fréchet JM. Acetalated dextran is a chemically and biologically tunable material for particulate immunotherapy. Proc Natl Acad Sci USA. 2009;106:5497–502.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Chen N, Gallovic MD, Tiet P, Ting JP, Ainslie KM, Bachelder EM. Investigation of tunable acetalated dextran microparticle platform to optimize M2e-based influenza vaccine efficacy. J Controlled Rel. 2018;289:114–24.

    Article  CAS  Google Scholar 

  28. Brown GD, Gordon S. Fungal beta-glucans and mammalian immunity. Immunity. 2003;19:311–5.

    Article  PubMed  CAS  Google Scholar 

  29. Sahasrabudhe NM, Dokter-Fokkens J, de Vos P. Particulate beta-glucans synergistically activate TLR4 and Dectin-1 in human dendritic cells. Mol Nutr Food Res. 2016;60:2514–22.

    Article  PubMed  CAS  Google Scholar 

  30. Li N, Zhang Y, Han M, Liu T, Wu J, Xiong Y, et al. Self-adjuvant Astragalus polysaccharide-based nanovaccines for enhanced tumor immunotherapy: a novel delivery system candidate for tumor vaccines. Sci China Life Sci. 2024;67:680–97.

    Article  PubMed  CAS  Google Scholar 

  31. Buonaguro L, Cavalluzzo B, Mauriello A, Ragone C, Tornesello AL, Buonaguro FM, et al. Microorganisms-derived antigens for preventive anti-cancer vaccines. Mol Asp Med. 2023;92:101192.

    Article  CAS  Google Scholar 

  32. Enokida T, Moreira A, Bhardwaj N. Vaccines for immunoprevention of cancer. J Clin Invest. 2021;131:e146956.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Paston SJ, Brentville VA, Symonds P, Durrant LG. Cancer vaccines, adjuvants, and delivery systems. Front Immunol. 2021;12:627932.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Hollingsworth RE, Jansen K. Turning the corner on therapeutic cancer vaccines. npj Vaccines. 2019;4:7.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Baert K, Sonck E, Goddeeris BM, Devriendt B, Cox E. Cell type-specific differences in beta-glucan recognition and signalling in porcine innate immune cells. Dev Comp Immunol. 2015;48:192–203.

    Article  PubMed  CAS  Google Scholar 

  36. Del Prete A, Salvi V, Soriani A, Laffranchi M, Sozio F, Bosisio D, et al. Dendritic cell subsets in cancer immunity and tumor antigen sensing. Cell Mol Immunol. 2023;20:432–47.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

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.

Author information

Author notes

  1. These authors contributed equally: Xiang He, Jiang-ling Lu, Wen-feng Liao

Authors and Affiliations

  1. Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Xiang He, Xing Zhang & Yi-fu Yang

  2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    Jiang-ling Lu, Wen-feng Liao, Yi-ru Long, Qian Zhu, Heng-lei Lu, Geng-yan Hao, Kan Ding, Jian-hua Sun & Li-kun Gong

  3. University of Chinese Academy of Sciences, Beijing, 100049, China

    Jiang-ling Lu, Wen-feng Liao, Yi-ru Long, Geng-yan Hao, Kan Ding, Jian-hua Sun & Li-kun Gong

  4. Zhongshan Institute for Drug Discovery, Institutes of Drug Discovery and Development Chinese Academy of Sciences, Zhongshan, 528400, China

    Jiang-ling Lu, Kan Ding & Li-kun Gong

Authors
  1. Xiang He
    View author publications

    Search author on:PubMed Google Scholar

  2. Jiang-ling Lu
    View author publications

    Search author on:PubMed Google Scholar

  3. Wen-feng Liao
    View author publications

    Search author on:PubMed Google Scholar

  4. Yi-ru Long
    View author publications

    Search author on:PubMed Google Scholar

  5. Xing Zhang
    View author publications

    Search author on:PubMed Google Scholar

  6. Qian Zhu
    View author publications

    Search author on:PubMed Google Scholar

  7. Heng-lei Lu
    View author publications

    Search author on:PubMed Google Scholar

  8. Geng-yan Hao
    View author publications

    Search author on:PubMed Google Scholar

  9. Kan Ding
    View author publications

    Search author on:PubMed Google Scholar

  10. Jian-hua Sun
    View author publications

    Search author on:PubMed Google Scholar

  11. Li-kun Gong
    View author publications

    Search author on:PubMed Google Scholar

  12. Yi-fu Yang
    View author publications

    Search author on:PubMed Google Scholar

Contributions

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.

Ethics declarations

Competing interests

The authors declare no competing interests.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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 45, 2394–2404 (2024). https://doi.org/10.1038/s41401-024-01330-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41401-024-01330-8

Keywords

Search

Advanced search

Quick links