番茄素作为多功能佐剂可增强mRNA疫苗应答

IF 10.2 1区 医学 Q1 ENGINEERING, BIOMEDICAL
Wen Xiao , Shugang Qin , Xuehui Li , Xinyang Jin , Aiwei Zhu , Xi He , Xing Duan , Yuting Chen , Yupei Zhang , Na Fan , Qian Zheng , Guohong Li , Zhongshan He , Kepan Chen , Hai Huang , Xiawei Wei , Christiane Moog , Bin Su , Xiangrong Song
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引用次数: 0

摘要

mRNA疫苗的有效适应性免疫应答需要从mRNA载体中翻译出足够的抗原并高效激活先天免疫。然而,尚不清楚是否简单引入佐剂可以帮助mRNA疫苗实现这些功能。本研究通过实验将天然产物番茄素掺入广泛应用的纳米载体中,作为一种多功能佐剂,提高mRNA表达效率,激活先天免疫。番茄素基脂质体(T-LPX)通过小泡蛋白介导的内吞作用在树突状细胞(DCs)中表现出更高的摄取,并通过番茄素介导的DExH-box解旋酶29的表达增加来改善mRNA的翻译,从而显著提高mRNA的表达效率并确保高效的抗原呈递。此外,番茄素被证明可以激活核苷酸结合寡聚化结构域(NOD)样受体通路,从而促进IFN-γ的分泌并上调dc中的共刺激分子(CD80和CD86)。最后,我们研究了负载肿瘤抗原编码mRNA的T-LPX,发现它能引发针对E.G7-OVA小鼠肿瘤的有效免疫应答。此外,番茄素的这种多功能佐剂作用也被证明同样适用于其他纳米载体(脂质纳米颗粒)和抗原。以番茄为基础的抗SARS-CoV-2 LNP-mRNA疫苗表现出持久的体液和细胞免疫反应。这些发现强调了番茄素作为mRNA纳米疫苗的多功能佐剂的潜力,在癌症治疗和传染病预防方面都有很好的应用前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Tomatine as a versatile adjuvant boosts mRNA vaccine responses

Tomatine as a versatile adjuvant boosts mRNA vaccine responses
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-γ 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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来源期刊
CiteScore
8.30
自引率
4.90%
发文量
303
审稿时长
30 days
期刊介绍: Materials Today Bio is a multidisciplinary journal that specializes in the intersection between biology and materials science, chemistry, physics, engineering, and medicine. It covers various aspects such as the design and assembly of new structures, their interaction with biological systems, functionalization, bioimaging, therapies, and diagnostics in healthcare. The journal aims to showcase the most significant advancements and discoveries in this field. As part of the Materials Today family, Materials Today Bio provides rigorous peer review, quick decision-making, and high visibility for authors. It is indexed in Scopus, PubMed Central, Emerging Sources, Citation Index (ESCI), and Directory of Open Access Journals (DOAJ).
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