{"title":"Microbiome Metabolite-Incorporated Lipid Nanoparticles Augment CD8<sup>+</sup> T Cell Memory Potential and Immunity for mRNA Cancer Vaccines.","authors":"Seok-Beom Yong, Minki Ha, Sungchan Cho","doi":"10.1021/acsbiomaterials.5c00738","DOIUrl":null,"url":null,"abstract":"<p><p>Recently, mRNA/lipid nanoparticle (LNP)-based vaccines have been successfully applied to prevent infectious diseases, and several types of neoantigen-encoding mRNA cancer vaccines are currently under clinical trials. While mRNA vaccines effectively induce adaptive immune responses to antigens, mRNA vaccine-induced immunity is shortly maintained, and the longevity of the immune memory, especially improving the CD8<sup>+</sup> T cell memory potential, could be even more important. Previously, microbiome metabolites have shown T cell memory potential-augmenting effects via regulating the immunometabolism. Herein, we develop microbiome metabolite-incorporated LNPs (mmi-LNPs) and evaluate their potential to enhance T cell memory responses following mRNA vaccination. In various ionizable LNP formulations, mmi-LNPs elicited more stem cell-like memory T cells (T-SCMs) and augmented central and effector memory T cell responses, which indicates the general applicability of mmi-LNPs. Notably, butyrate-incorporated mmi-LNP exhibited the strongest effects. In conclusion, we suggest microbiome metabolite-incorporated LNP as a next-generation delivery vehicle for mRNA vaccines.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"4254-4265"},"PeriodicalIF":5.5000,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Biomaterials Science & Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1021/acsbiomaterials.5c00738","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/9 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
Recently, mRNA/lipid nanoparticle (LNP)-based vaccines have been successfully applied to prevent infectious diseases, and several types of neoantigen-encoding mRNA cancer vaccines are currently under clinical trials. While mRNA vaccines effectively induce adaptive immune responses to antigens, mRNA vaccine-induced immunity is shortly maintained, and the longevity of the immune memory, especially improving the CD8+ T cell memory potential, could be even more important. Previously, microbiome metabolites have shown T cell memory potential-augmenting effects via regulating the immunometabolism. Herein, we develop microbiome metabolite-incorporated LNPs (mmi-LNPs) and evaluate their potential to enhance T cell memory responses following mRNA vaccination. In various ionizable LNP formulations, mmi-LNPs elicited more stem cell-like memory T cells (T-SCMs) and augmented central and effector memory T cell responses, which indicates the general applicability of mmi-LNPs. Notably, butyrate-incorporated mmi-LNP exhibited the strongest effects. In conclusion, we suggest microbiome metabolite-incorporated LNP as a next-generation delivery vehicle for mRNA vaccines.
期刊介绍：
ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics:
Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology
Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions
Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis
Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering
Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends
Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring
Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration
Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials
Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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