• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

锰配位 mRNA 疫苗具有增强的 mRNA 表达和免疫原性，可诱导针对 SARS-CoV-2 变体的强大免疫应答。

Manganese-coordinated mRNA vaccines with enhanced mRNA expression and immunogenicity induce robust immune responses against SARS-CoV-2 variants.

机构信息

Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

WestChina-Frontier PharmaTech Co. Ltd., Chengdu, Sichuan, China.

出版信息

Sci Adv. 2022 Dec 23;8(51):eabq3500. doi: 10.1126/sciadv.abq3500.

DOI:10.1126/sciadv.abq3500
PMID:36563159
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9788765/
Abstract

It is urgent to develop more effective mRNA vaccines against the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants owing to the immune escape. Here, we constructed a novel mRNA delivery system [IC8/Mn lipid nanoparticles (IC8/Mn LNPs)]with high immunogenicity, via introducing a stimulator of interferon genes (STING) agonist [manganese (Mn)] based on a newly synthesized ionizable lipid (IC8). It was found that Mn can not only promote maturation of antigen-presenting cells via activating STING pathway but also improve mRNA expression by facilitating lysosomal escape for the first time. Subsequently, IC8/Mn LNPs loaded with mRNA encoding the Spike protein of SARS-CoV-2 Delta or Omicron variant (IC8/Mn@D or IC8/Mn@O) were prepared. Both mRNA vaccines induced substantial specific immunoglobulin G responses against Delta or Omicron. IC8/Mn@D displayed strong pseudovirus neutralization ability, T helper 1-biased immune responses, and good safety. It can be concluded that IC8/Mn LNPs have great potential for developing Mn-coordinated mRNA vaccines with robust immunogenicity and good safety.

摘要

由于免疫逃逸，开发针对新兴的严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 变体的更有效的 mRNA 疫苗迫在眉睫。在这里，我们构建了一种新型的 mRNA 传递系统 [IC8/Mn 脂质纳米粒（IC8/Mn LNPs）]，通过在新合成的可离子化脂质（IC8）的基础上引入干扰素基因刺激物（STING）激动剂 [锰（Mn）]，具有高免疫原性。研究发现，Mn 不仅可以通过激活 STING 通路促进抗原呈递细胞的成熟，而且还可以首次通过促进溶酶体逃逸来提高 mRNA 的表达。随后，制备了负载编码 SARS-CoV-2 Delta 或 Omicron 变体的 Spike 蛋白的 mRNA 的 IC8/Mn LNPs（IC8/Mn@D 或 IC8/Mn@O）。这两种 mRNA 疫苗都能诱导针对 Delta 或 Omicron 的大量特异性免疫球蛋白 G 反应。IC8/Mn@D 显示出强大的假病毒中和能力、Th1 偏向性免疫反应和良好的安全性。可以得出结论，IC8/Mn LNPs 具有很大的潜力，可用于开发具有强大免疫原性和良好安全性的 Mn 协调的 mRNA 疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/c79fb2673f58/sciadv.abq3500-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/3ee220f3fb57/sciadv.abq3500-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/35e3b6ced8a0/sciadv.abq3500-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/4239df11a272/sciadv.abq3500-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/fa6f854e4b99/sciadv.abq3500-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/28400837673a/sciadv.abq3500-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/b8a2cc820108/sciadv.abq3500-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/c79fb2673f58/sciadv.abq3500-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/3ee220f3fb57/sciadv.abq3500-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/35e3b6ced8a0/sciadv.abq3500-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/4239df11a272/sciadv.abq3500-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/fa6f854e4b99/sciadv.abq3500-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/28400837673a/sciadv.abq3500-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/b8a2cc820108/sciadv.abq3500-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fc/9788765/c79fb2673f58/sciadv.abq3500-f7.jpg

相似文献

1
Manganese-coordinated mRNA vaccines with enhanced mRNA expression and immunogenicity induce robust immune responses against SARS-CoV-2 variants.锰配位 mRNA 疫苗具有增强的 mRNA 表达和免疫原性，可诱导针对 SARS-CoV-2 变体的强大免疫应答。
Sci Adv. 2022 Dec 23;8(51):eabq3500. doi: 10.1126/sciadv.abq3500.
2
mRNA Vaccines Against SARS-CoV-2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids.基于新型可电离脂质的脂质纳米颗粒递送的抗SARS-CoV-2变体的mRNA疫苗
Adv Funct Mater. 2022 Sep 26;32(39):2204692. doi: 10.1002/adfm.202204692. Epub 2022 Jul 19.
3
Bivalent mRNA vaccines against three SARS-CoV-2 variants mediated by new ionizable lipid nanoparticles.针对三种 SARS-CoV-2 变异株的双价 mRNA 疫苗，由新型可离子化脂质纳米粒介导。
Int J Pharm. 2023 Jul 25;642:123155. doi: 10.1016/j.ijpharm.2023.123155. Epub 2023 Jul 2.
4
Adjuvant lipidoid-substituted lipid nanoparticles augment the immunogenicity of SARS-CoV-2 mRNA vaccines.佐剂脂质纳米颗粒增强了 SARS-CoV-2 mRNA 疫苗的免疫原性。
Nat Nanotechnol. 2023 Sep;18(9):1105-1114. doi: 10.1038/s41565-023-01404-4. Epub 2023 Jun 26.
5
Boosting with Multiple Doses of mRNA Vaccine after Priming with Two Doses of Protein Subunit Vaccine MVC-COV1901 Elicited Robust Humoral and Cellular Immune Responses against Emerging SARS-CoV-2 Variants.两剂蛋白亚单位疫苗 MVC-COV1901 初免后加强接种多剂 mRNA 疫苗可增强针对新型 SARS-CoV-2 变异株的体液和细胞免疫应答。
Microbiol Spectr. 2022 Oct 26;10(5):e0060922. doi: 10.1128/spectrum.00609-22. Epub 2022 Aug 25.
6
STING Agonist-Derived LNP-mRNA Vaccine Enhances Protective Immunity Against SARS-CoV-2.STING 激动剂衍生的 LN P-mRNA 疫苗增强了对 SARS-CoV-2 的保护性免疫。
Nano Lett. 2023 Apr 12;23(7):2593-2600. doi: 10.1021/acs.nanolett.2c04883. Epub 2023 Mar 21.
7
Novel Ionizable Lipid Nanoparticles for SARS-CoV-2 Omicron mRNA Delivery.新型可离子化脂质纳米颗粒用于 SARS-CoV-2 奥密克戎 mRNA 递送。
Adv Healthc Mater. 2023 May;12(13):e2202590. doi: 10.1002/adhm.202202590. Epub 2023 Feb 17.
8
Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2.mRNA 疫苗的免疫原性机制及其在促进 SARS-CoV-2 适应性保护方面的局限性。
PeerJ. 2022 Mar 9;10:e13083. doi: 10.7717/peerj.13083. eCollection 2022.
9
Neutralizing Potency of Prototype and Omicron RBD mRNA Vaccines Against Omicron Variant.原型株和奥密克戎 RBD mRNA 疫苗对奥密克戎变异株中和效力。
Front Immunol. 2022 Jun 30;13:908478. doi: 10.3389/fimmu.2022.908478. eCollection 2022.
10
A self-amplifying mRNA SARS-CoV-2 vaccine candidate induces safe and robust protective immunity in preclinical models.一种自我扩增的 SARS-CoV-2 mRNA 疫苗候选物在临床前模型中诱导安全、强大的保护性免疫。
Mol Ther. 2022 May 4;30(5):1897-1912. doi: 10.1016/j.ymthe.2022.01.001. Epub 2022 Jan 3.

引用本文的文献

1
Endo/Lysosomal-Escapable Lipid Nanoparticle Platforms for Enhancing mRNA Delivery in Cancer Therapy.用于增强癌症治疗中mRNA递送的可逃逸至内体/溶酶体的脂质纳米颗粒平台
Pharmaceutics. 2025 Jun 20;17(7):803. doi: 10.3390/pharmaceutics17070803.
2
Eliciting antitumor immunity via therapeutic cancer vaccines.通过治疗性癌症疫苗激发抗肿瘤免疫力。
Cell Mol Immunol. 2025 Jul 9. doi: 10.1038/s41423-025-01316-4.
3
Membrane-IL12 adjuvant mRNA vaccine polarizes pre-effector T cells for optimized tumor control.膜结合白细胞介素-12佐剂mRNA疫苗使前效应T细胞极化以优化肿瘤控制。

本文引用的文献

1
mRNA Vaccines Against SARS-CoV-2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids.基于新型可电离脂质的脂质纳米颗粒递送的抗SARS-CoV-2变体的mRNA疫苗
Adv Funct Mater. 2022 Sep 26;32(39):2204692. doi: 10.1002/adfm.202204692. Epub 2022 Jul 19.
2
Estimates of SARS-CoV-2 Omicron Variant Severity in Ontario, Canada.加拿大安大略省估计 SARS-CoV-2 奥密克戎变异株的严重程度。
JAMA. 2022 Apr 5;327(13):1286-1288. doi: 10.1001/jama.2022.2274.
3
Delayed-interval BNT162b2 mRNA COVID-19 vaccination enhances humoral immunity and induces robust T cell responses.
J Exp Med. 2025 Sep 1;222(9). doi: 10.1084/jem.20241454. Epub 2025 Jun 6.
4
Tumor microenvironment-activated Zn//MnO battery for sustained and local electrochemical immunotherapy.用于持续和局部电化学免疫治疗的肿瘤微环境激活的锌//锰氧化物电池
Sci Adv. 2025 May 30;11(22):eadu1647. doi: 10.1126/sciadv.adu1647. Epub 2025 May 28.
5
MHCI trafficking signal-based mRNA vaccines strengthening immune protection against RNA viruses.基于MHC I类分子转运信号的mRNA疫苗增强针对RNA病毒的免疫保护。
Bioeng Transl Med. 2024 Aug 15;10(1):e10709. doi: 10.1002/btm2.10709. eCollection 2025 Jan.
6
Pioneering integration of combinatorial chemistry and machine learning to accelerate the development of tailored LNPs for mRNA delivery.开创性地将组合化学与机器学习相结合，以加速用于mRNA递送的定制脂质纳米颗粒的开发。
Acta Pharm Sin B. 2024 Nov;14(11):5079-5081. doi: 10.1016/j.apsb.2024.08.032. Epub 2024 Sep 2.
7
IL-7 promotes mRNA vaccine-induced long-term immunity.白细胞介素-7 促进 mRNA 疫苗诱导的长期免疫。
J Nanobiotechnology. 2024 Nov 16;22(1):716. doi: 10.1186/s12951-024-02993-5.
8
2D Differential Metallic Immunopotentiators Drive High Diversity and Capability of Antigen-specific Immunity Against Tumor.2D 差分金属免疫增强剂可驱动针对肿瘤的抗原特异性免疫的高多样性和高能力。
Adv Sci (Weinh). 2024 Oct;11(40):e2405729. doi: 10.1002/advs.202405729. Epub 2024 Sep 3.
9
Recent Advancements in mRNA Vaccines: From Target Selection to Delivery Systems.mRNA疫苗的最新进展：从靶点选择到递送系统
Vaccines (Basel). 2024 Aug 1;12(8):873. doi: 10.3390/vaccines12080873.
10
Lipoplexes' Structure, Preparation, and Role in Managing Different Diseases.脂质体的结构、制备及其在治疗多种疾病中的作用。
AAPS PharmSciTech. 2024 Jun 7;25(5):131. doi: 10.1208/s12249-024-02850-6.
延迟间隔 BNT162b2 mRNA COVID-19 疫苗接种可增强体液免疫并诱导强烈的 T 细胞反应。
Nat Immunol. 2022 Mar;23(3):380-385. doi: 10.1038/s41590-021-01126-6. Epub 2022 Feb 3.
4
Delivery Strategies for mRNA Vaccines.mRNA 疫苗的递送策略。
Pharmaceut Med. 2022 Feb;36(1):11-20. doi: 10.1007/s40290-021-00417-5. Epub 2022 Jan 30.
5
Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.南非对 SARS-CoV-2 奥密克戎变异株临床严重程度的早期评估：一项数据关联研究。
Lancet. 2022 Jan 29;399(10323):437-446. doi: 10.1016/S0140-6736(22)00017-4. Epub 2022 Jan 19.
6
Transmission from vaccinated individuals in a large SARS-CoV-2 Delta variant outbreak.接种疫苗者在 SARS-CoV-2 德尔塔变异株大流行中的传播。
Cell. 2022 Feb 3;185(3):485-492.e10. doi: 10.1016/j.cell.2021.12.027. Epub 2021 Dec 23.
7
SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein-ACE2 complex.SARS-CoV-2 奥密克戎变异株：刺突蛋白-ACE2 复合物的抗体逃逸和冷冻电镜结构。
Science. 2022 Feb 18;375(6582):760-764. doi: 10.1126/science.abn7760. Epub 2022 Jan 20.
8
Effectiveness of mRNA-1273 against delta, mu, and other emerging variants of SARS-CoV-2: test negative case-control study.mRNA-1273 对德尔塔、缪和其他 SARS-CoV-2 新兴变异株的有效性：核酸检测阴性的病例对照研究。
BMJ. 2021 Dec 15;375:e068848. doi: 10.1136/bmj-2021-068848.
9
Zwitterionic Phospholipidation of Cationic Polymers Facilitates Systemic mRNA Delivery to Spleen and Lymph Nodes.两性离子磷脂化阳离子聚合物有助于系统递送 mRNA 至脾脏和淋巴结。
J Am Chem Soc. 2021 Dec 22;143(50):21321-21330. doi: 10.1021/jacs.1c09822. Epub 2021 Dec 8.
10
Delivery of STING agonists for adjuvanting subunit vaccines.STING 激动剂在佐剂亚单位疫苗中的递送。
Adv Drug Deliv Rev. 2021 Dec;179:114020. doi: 10.1016/j.addr.2021.114020. Epub 2021 Oct 29.