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文献精选 > 近年高分"mRNA疫苗"研究（IF≥30，近5年）

Advances in COVID-19 mRNA vaccine development. ​

文献信息 ​

DOI10.1038/s41392-022-00950-y
PMID35322018
期刊Signal transduction and targeted therapy
影响因子52.7
JCR 分区Q1
发表年份2022
被引次数240
关键词COVID-19, mRNA疫苗, 疫苗开发
文献类型Journal Article, Review
ISSN2059-3635
页码94
期号7(1)
作者Enyue Fang, Xiaohui Liu, Miao Li, Zelun Zhang, Lifang Song, Baiyu Zhu, Xiaohong Wu, Jingjing Liu, Danhua Zhao, Yuhua Li

一句话小结 ​

本综述文章探讨了COVID-19 mRNA疫苗的技术优势及其在疫情控制中的重要性，指出mRNA疫苗具有快速开发、适应新变种和优良免疫反应等特点。通过总结相关结构特征、抗原设计、递送系统及临床试验数据，文章还分析了当前发展中的挑战与未来方向，强调了其在公共卫生中的潜在贡献。

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COVID-19 · mRNA疫苗 · 疫苗开发

摘要 ​

截至目前，由严重急性呼吸综合症冠状病毒2型（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）已在全球确诊399,600,607例病例，并导致5,757,562人死亡。COVID-19对全球人类健康构成了严重威胁。世界卫生组织（WHO）已将COVID-19大流行宣告为重大的公共卫生紧急事件。疫苗接种是控制疫情传播、拯救生命和保护人群健康的最有效和经济的干预措施。在COVID-19疫苗的开发中，采用了多种技术。其中，COVID-19信使RNA（mRNA）疫苗因其巨大的应用前景和优势而受到越来越多的关注，这些优势包括开发周期短、工业化容易、生产过程简单、对新变种的适应性强以及能够诱导更好的免疫反应。本综述总结了关于COVID-19 mRNA疫苗及mRNA技术的结构特征、抗原设计策略、递送系统、工业化潜力、质量控制、最新临床试验和真实世界数据的当前知识。同时，还讨论了在主要传染病预防性mRNA疫苗开发中的当前挑战和未来方向。

英文摘要 ​

To date, the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has determined 399,600,607 cases and 5,757,562 deaths worldwide. COVID-19 is a serious threat to human health globally. The World Health Organization (WHO) has declared COVID-19 pandemic a major public health emergency. Vaccination is the most effective and economical intervention for controlling the spread of epidemics, and consequently saving lives and protecting the health of the population. Various techniques have been employed in the development of COVID-19 vaccines. Among these, the COVID-19 messenger RNA (mRNA) vaccine has been drawing increasing attention owing to its great application prospects and advantages, which include short development cycle, easy industrialization, simple production process, flexibility to respond to new variants, and the capacity to induce better immune response. This review summarizes current knowledge on the structural characteristics, antigen design strategies, delivery systems, industrialization potential, quality control, latest clinical trials and real-world data of COVID-19 mRNA vaccines as well as mRNA technology. Current challenges and future directions in the development of preventive mRNA vaccines for major infectious diseases are also discussed.

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主要研究问题 ​

  1. COVID-19 mRNA疫苗在应对新变种方面的具体优势是什么？
  2. 除了mRNA疫苗，还有哪些新兴疫苗技术正在开发中，可能会与mRNA技术竞争？
  3. 在mRNA疫苗的工业化过程中，存在哪些主要的技术和生产挑战？
  4. 当前mRNA疫苗在临床试验中的表现如何，与传统疫苗相比有何不同？
  5. 针对其他传染病，mRNA技术的应用前景如何，存在哪些潜在的障碍？

核心洞察 ​

研究背景和目的 ​

新冠病毒病（COVID-19）由严重急性呼吸综合症冠状病毒2型（SARS-CoV-2）引起，已造成全球数亿病例和数百万死亡。世界卫生组织（WHO）将其视为重大公共卫生紧急事件。疫苗接种是控制疫情传播、拯救生命和保护公众健康的最有效经济手段。本综述旨在总结COVID-19 mRNA疫苗的结构特征、抗原设计策略、递送系统、工业化潜力、质量控制、最新临床试验及现实数据，并探讨mRNA技术在主要传染病预防疫苗开发中的挑战和未来方向。

主要方法/材料/实验设计 ​

本研究采用文献综述的方法，分析了不同类型的mRNA疫苗，包括非复制mRNA、自我扩增mRNA（saRNA）和环状RNA（circRNA），并讨论了其生产过程、递送系统及免疫应答机制。

Mermaid diagram

关键结果和发现 ​

  1. 疫苗类型：

    • 非复制mRNA：直接编码目标抗原，具有较短的结构和较高的生物活性。
    • 自我扩增mRNA：通过编码病毒RNA聚合酶实现自我复制，潜在提高抗原表达。
    • 环状RNA：因其稳定性高，具有较长的半衰期和免疫应答优势。

  2. 生产与递送：

    • mRNA疫苗的生产不需要细胞培养，生产周期短，适合快速工业化。
    • 常用的递送系统为脂质纳米颗粒（LNP），能够有效包裹mRNA并促进细胞内释放。

  3. 免疫应答：

    • mRNA疫苗能够诱导强烈的体液免疫和细胞免疫反应，尤其是针对SARS-CoV-2的S蛋白。

主要结论/意义/创新性 ​

mRNA疫苗技术为快速应对新兴传染病提供了新的解决方案。与传统疫苗相比，mRNA疫苗具有开发周期短、生产简单和免疫应答强等优势。COVID-19 mRNA疫苗的成功开发为未来疫苗技术的进步奠定了基础，并可能推动其他传染病和癌症的疫苗研发。

研究局限性和未来方向 ​

  • 局限性：当前mRNA疫苗的存储和运输要求超低温，给全球分发带来挑战。此外，长期免疫保护的持续性仍需进一步研究。
  • 未来方向：未来的研究应集中在提高mRNA疫苗的稳定性、开发新型递送系统和优化抗原设计，以应对病毒变异和提高疫苗的普遍适应性。

此综述为COVID-19 mRNA疫苗的研发和应用提供了全面的概述，并为未来的疫苗开发提供了重要的参考。

参考文献 ​

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  9. Myocarditis after Covid-19 Vaccination in a Large Health Care Organization. - Guy Witberg;Noam Barda;Sara Hoss;Ilan Richter;Maya Wiessman;Yaron Aviv;Tzlil Grinberg;Oren Auster;Noa Dagan;Ran D Balicer;Ran Kornowski - The New England journal of medicine (2021)
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引用本文的文献 ​

  1. COVID-19 vaccine development: milestones, lessons and prospects. - Maochen Li;Han Wang;Lili Tian;Zehan Pang;Qingkun Yang;Tianqi Huang;Junfen Fan;Lihua Song;Yigang Tong;Huahao Fan - Signal transduction and targeted therapy (2022)
  2. Development of DNA Vaccine Candidate against SARS-CoV-2. - Xingyun Wang;Nino Rcheulishvili;Jie Cai;Cong Liu;Fengfei Xie;Xing Hu;Nuo Yang;Mengqi Hou;Dimitri Papukashvili;Yunjiao He;Peng George Wang - Viruses (2022)
  3. Recent Progress in Recombinant Influenza Vaccine Development Toward Heterosubtypic Immune Response. - Mark B Carascal;Rance Derrick N Pavon;Windell L Rivera - Frontiers in immunology (2022)
  4. Advances in nanotechnology application in biosafety materials: A crucial response to COVID-19 pandemic. - Rasmi V Morajkar;Akhil S Kumar;Rohan K Kunkalekar;Amit A Vernekar - Biosafety and health (2022)
  5. Lipid nanoparticles in the development of mRNA vaccines for COVID-19. - Barnabas Wilson;Kannoth Mukundan Geetha - Journal of drug delivery science and technology (2022)
  6. Message in a bottle: mRNA vaccination for influenza. - Jessica R Shartouny;Anice C Lowen - The Journal of general virology (2022)
  7. Current Evidence in SARS-CoV-2 mRNA Vaccines and Post-Vaccination Adverse Reports: Knowns and Unknowns. - Dimitra S Mouliou;Efthimios Dardiotis - Diagnostics (Basel, Switzerland) (2022)
  8. Clinical and Molecular Characterization of a Rare Case of BNT162b2 mRNA COVID-19 Vaccine-Associated Myositis. - Eli Magen;Sumit Mukherjee;Mahua Bhattacharya;Rajesh Detroja;Eugene Merzon;Idan Blum;Alejandro Livoff;Mark Shlapobersky;Gideon Baum;Ran Talisman;Evgenia Cherniavsky;Amir Dori;Milana Frenkel-Morgenstern - Vaccines (2022)
  9. Meeting the Need for a Discussion of Unmet Medical Need. - Denis Horgan;Bettina Borisch;Bogi Eliasen;Peter Kapitein;Andrew V Biankin;Stefan Gijssels;Michael Zaiac;Marie-Helene Fandel;Jonathan A Lal;Marta Kozaric;Barbara Moss;Ruggero De Maria;Marius Geanta;Frédérique Nowak;Antoni Montserrat-Moliner;Olaf Riess - Healthcare (Basel, Switzerland) (2022)
  10. The Delivery of mRNA Vaccines for Therapeutics. - Nitika;Jiao Wei;Ai-Min Hui - Life (Basel, Switzerland) (2022)

... (230 更多 篇文献)

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