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Tomatine as a versatile adjuvant boosts mRNA vaccine responses

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机构: [1]Sichuan Univ, West China Hosp, Dept Crit Care Med, Chengdu 610000, Peoples R China [2]Sichuan Univ, West China Hosp, Canc Ctr Dept Biotherapy, Frontiers Sci Ctr Dis Related Mol Network, Chengdu 610000, Peoples R China [3]Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610000, Peoples R China [4]Army Med Univ, Coll Basic Med, Dept Biosafety, Chongqing 404100, Peoples R China [5]Univ Elect Sci & Technol China, Sichuan Canc Hosp Inst, Sichuan Clin Res Ctr Canc, Sichuan Canc Ctr,Affiliated Canc Hosp,Dept Expt Re, Chengdu, Peoples R China [6]Guizhou Med Univ, Affiliated Hosp, Ctr Clin Labs, Sch Clin Lab Sci, Guiyang 550004, Peoples R China [7]Macau Univ Sci & Technol, Fac Med, Sch Pharm, Macau 999078, Peoples R China [8]Capital Med Univ, Beijing Youan Hosp, Beijing Key Lab HIV AIDS Res, Sino French Joint Lab HIV AIDS Res, Beijing 100069, Peoples R China [9]Univ Strasbourg, Federat Med Translat Strasbourg FMTS,Inst Themat I, INSERM,UMRS 1109,Transplantex NG,Fac Med, Federat Hosp Univ OMICARE,Lab ImmunoRhumatol Mol, F-67000 Strasbourg, France [10]Vaccine Res Inst VRI, F-94000 Creteil, France [11]Capital Med Univ, Beijing Youan Hosp, Cent Lab, Beijing 100069, Peoples R China
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关键词: mRNA vaccine Adjuvant Tomatine mRNA expression Immunogenicity Nano-carrier

摘要:
The potent adaptive immune response of mRNA vaccines requires that sufficient antigens translated from mRNA cargos and highly efficient activation of innate immunity. However, it remains unclear if simple introduction of an adjuvant can help mRNA vaccines achieve these functions. In this study, a nature product, tomatine, was experimentally incorporated into the widely used nanocarriers, serving a multi-functional adjuvant to improve mRNA expression efficiency and activate innate immunity. Tomatine based liposome (T-LPX) exhibited elevated uptake in dendritic cells (DCs) via caveolin-mediated endocytosis and improved mRNA translation via the increased expression of DExH-box helicase 29 mediated by tomatine, leading to a marked increase in mRNA expression efficiency and ensuring highly efficient antigen presentation. Additionally, tomatine was shown to activate nucleotide-binding oligomerization domain (NOD)-like receptor pathway, thereby promoting the secretion of IFN-gamma and upregulating the co-stimulatory molecules (CD80 and CD86) in DCs. Finally, T-LPX loaded with a tumor antigen-encoding mRNA was investigated and found to elicit potent immune responses against the E.G7-OVA murine tumor. Furthermore, such versatile adjuvant effect of tomatine was also demonstrated to equally apply to the other nanocarrier (lipid nanoparticle) and antigen. The tomatine-based LNP-mRNA vaccine against SARS-CoV-2 presented enduring humoral and cellular immune responses. These findings underscore tomatine's potential as a versatile adjuvant for mRNA nano-vaccines, with promising applications in both cancer therapy and infectious disease prevention.

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出版当年[2025]版:
大类 | 1 区 医学
小类 | 1 区 材料科学:生物材料 2 区 工程:生物医学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 材料科学:生物材料 2 区 工程:生物医学
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Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS
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Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS

影响因子: 最新[2024版] 最新五年平均 出版当年[2024版] 出版当年五年平均 出版前一年[2024版]

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第一作者机构: [1]Sichuan Univ, West China Hosp, Dept Crit Care Med, Chengdu 610000, Peoples R China [2]Sichuan Univ, West China Hosp, Canc Ctr Dept Biotherapy, Frontiers Sci Ctr Dis Related Mol Network, Chengdu 610000, Peoples R China [3]Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610000, Peoples R China [4]Army Med Univ, Coll Basic Med, Dept Biosafety, Chongqing 404100, Peoples R China
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通讯机构: [1]Sichuan Univ, West China Hosp, Dept Crit Care Med, Chengdu 610000, Peoples R China [2]Sichuan Univ, West China Hosp, Canc Ctr Dept Biotherapy, Frontiers Sci Ctr Dis Related Mol Network, Chengdu 610000, Peoples R China [3]Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610000, Peoples R China [8]Capital Med Univ, Beijing Youan Hosp, Beijing Key Lab HIV AIDS Res, Sino French Joint Lab HIV AIDS Res, Beijing 100069, Peoples R China [9]Univ Strasbourg, Federat Med Translat Strasbourg FMTS,Inst Themat I, INSERM,UMRS 1109,Transplantex NG,Fac Med, Federat Hosp Univ OMICARE,Lab ImmunoRhumatol Mol, F-67000 Strasbourg, France [10]Vaccine Res Inst VRI, F-94000 Creteil, France [11]Capital Med Univ, Beijing Youan Hosp, Cent Lab, Beijing 100069, Peoples R China
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