机构:[1]Sichuan Univ, West China Hosp, Dept Crit Care Med, Chengdu 610000, Peoples R China四川大学华西医院[2]Sichuan Univ, West China Hosp, Canc Ctr Dept Biotherapy, Frontiers Sci Ctr Dis Related Mol Network, Chengdu 610000, Peoples R China四川大学华西医院[3]Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610000, Peoples R China四川大学华西医院[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四川省肿瘤医院[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
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.
基金:
National Key Research and Development Program of China [2023YFC3403200, 2023YFC2308300, 2023YFE0116000]; National Natural Science Foundation of China [82300113]; China Postdoctoral Science Foundation [2022M722269]; Beijing Key Laboratory for HIV/AIDS Research [BZ0089]; Sichuan University Postdoctoral Interdisciplinary Innovation Fund [JCXK2204]; Post Doctor Research Project, West China Hospital, Sichuan University [2023HXBH015]; Sichuan Provincial Science and Technology Innovation (Seedling Project) Cultivation Projects [MZGC20230034]
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
共同第一作者:
通讯作者:
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
推荐引用方式(GB/T 7714):
Xiao Wen,Qin Shugang,Li Xuehui,et al.Tomatine as a versatile adjuvant boosts mRNA vaccine responses[J].MATERIALS TODAY BIO.2025,35:doi:10.1016/j.mtbio.2025.102360.
APA:
Xiao, Wen,Qin, Shugang,Li, Xuehui,Jin, Xinyang,Zhu, Aiwei...&Song, Xiangrong.(2025).Tomatine as a versatile adjuvant boosts mRNA vaccine responses.MATERIALS TODAY BIO,35,
MLA:
Xiao, Wen,et al."Tomatine as a versatile adjuvant boosts mRNA vaccine responses".MATERIALS TODAY BIO 35.(2025)