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

作　　者：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 

机构地区：[1]Experiment Center for Science and Technology,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China [2]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China [3]University of Chinese Academy of Sciences,Beijing,100049,China [4]Zhongshan Institute for Drug Discovery,Institutes of Drug Discovery and Development Chinese Academy of Sciences,Zhongshan,528400,China

出　　处：《Acta Pharmacologica Sinica》2024年第11期2394-2404,共11页中国药理学报（英文版）

基　　金：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);the National Science Foundation for Distinguished Young Scholars of China(32271332);supported by the Zhongshan Municipal Bureau of Science and Technology(CXTD2023010);Department of Science and Technology of Guangdong Province(High-level Innovative Research Institute 2021B0909050003).

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 homogeneousβ-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 pot

关 键 词：cancer vaccine ADJUVANT granola frondose polysaccharide GFPBW1 Β-GLUCAN 

分 类 号：R186[医药卫生—流行病学]