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

摘要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(5,50,500μg/mL)dose-dependently promoted activation and maturation of APCs in vitro by increasing CD80,CD86 and MHCⅡ expression.We immunized female mice with OVA in combination with GFPBW1(50 or 300 pg)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 lgG2b,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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作者 Xiang He [1] Jiang-ling Lu [2] Wen-feng Liao [3] Yi-ru Long [3] Xing Zhang [1] Qian Zhu [4] Heng-lei Lu [4] Geng-yan Hao [3] Kan Ding [2] Jian-hua Sun [3] Li-kun Gong [2] Yi-fu Yang [1] 学术成果认领
作者单位 Experiment Center for Science and Technology,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China [1] State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;University of Chinese Academy of Sciences,Beijing 100049,China;Zhongshan Institute for Drug Discovery,Institutes of Drug Discovery and Development Chinese Academy of Sciences,Zhongshan 528400,China [2] State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;University of Chinese Academy of Sciences,Beijing 100049,China [3] State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [4]
栏目名称 Immunopharmacology and Inflammation
DOI 10.1038/s41401-024-01330-8
发布时间 2024-11-26
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中国药理学报(英文版)

中国药理学报(英文版)

2024年45卷11期

2394-2404页

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