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Advances in mRNA Vaccines for Infectious Diseases. ​

文献信息 ​

DOI10.3389/fimmu.2019.00594
PMID30972078
期刊Frontiers in immunology
影响因子5.9
JCR 分区Q1
发表年份2019
被引次数353
关键词应用, 传递, 传染病, mRNA疫苗, 机制
文献类型Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN1664-3224
页码594
期号10()
作者Cuiling Zhang, Giulietta Maruggi, Hu Shan, Junwei Li

一句话小结 ​

该文献综述了RNA基础技术在疫苗开发中的重要进展，特别是mRNA疫苗在提供安全且持久免疫反应方面的临床前和临床试验成果。研究显示，mRNA疫苗不仅拥有快速生产的潜力，还有望成为有效对抗传染病的重要工具，展现了其未来设计和应用的广阔前景。

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应用 · 传递 · 传染病 · mRNA疫苗 · 机制

摘要 ​

在过去的二十年中，RNA基础技术在预防性和治疗性疫苗开发方面引起了广泛关注。临床前和临床试验表明，mRNA疫苗能够在动物模型和人类中提供安全且持久的免疫反应。在本综述中，我们总结了当前mRNA疫苗的研究进展，这些疫苗具有快速生产的潜力，并有望成为对抗传染病的强大工具，同时我们也强调了它们设计和应用的光明未来。

英文摘要 ​

During the last two decades, there has been broad interest in RNA-based technologies for the development of prophylactic and therapeutic vaccines. Preclinical and clinical trials have shown that mRNA vaccines provide a safe and long-lasting immune response in animal models and humans. In this review, we summarize current research progress on mRNA vaccines, which have the potential to be quick-manufactured and to become powerful tools against infectious disease and we highlight the bright future of their design and applications.

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主要研究问题 ​

  1. mRNA疫苗在预防特定传染病（如流感或新冠病毒）方面的效果如何？
  2. 除了传染病，mRNA技术在其他疾病（如癌症）中的应用前景如何？
  3. 目前有哪些主要的临床试验正在进行，专注于mRNA疫苗的开发和评估？
  4. 在mRNA疫苗的生产过程中，哪些技术创新正在被探索以提高效率和安全性？
  5. mRNA疫苗的长期免疫效果与传统疫苗相比有哪些优势和劣势？

核心洞察 ​

研究背景和目的 ​

mRNA疫苗作为一种新兴的疫苗平台，近年来受到广泛关注。其在预防和治疗传染病方面展现出良好的潜力，尤其是在快速应对疫情方面。本文旨在总结mRNA疫苗的研究进展，探讨其设计、应用及未来的发展方向。

主要方法/材料/实验设计 ​

本文采用文献综述的方法，系统分析了mRNA疫苗的机制、优缺点、生产工艺及其在不同传染病中的应用。以下是mRNA疫苗的技术路线示意图：

Mermaid diagram

关键结果和发现 ​

  1. mRNA疫苗的优势：非感染性、快速生产、可扩展性强，且不易整合入宿主基因组。
  2. 不同类型的mRNA疫苗：
    • 常规mRNA疫苗：通过直接转染产生抗原。
    • 自复制mRNA疫苗：可在宿主细胞内自我复制，产生更高水平的抗原表达。
  3. 免疫反应机制：mRNA疫苗通过激活TLR和RIG-I等内源性免疫传感器，诱导强烈的T细胞和B细胞免疫反应。

主要结论/意义/创新性 ​

mRNA疫苗代表了一种灵活且高效的疫苗开发平台，能够迅速应对新出现的传染病。其在COVID-19大流行期间的成功应用证明了其有效性和实用性。未来，mRNA疫苗有潜力扩展至癌症免疫治疗和过敏原去敏感化等领域。

研究局限性和未来方向 ​

尽管mRNA疫苗展现出良好的免疫原性和安全性，但仍面临一些挑战：

  • 稳定性问题：mRNA在体内易降解，需优化递送系统。
  • 免疫应答的个体差异：不同人群对mRNA疫苗的反应可能不同，需要进一步研究。
  • 生产成本和规模化问题：需提升生产工艺以降低成本，实现大规模生产。

未来的研究应集中在提高mRNA疫苗的稳定性、优化递送系统、深入理解其免疫机制，以及扩展其应用范围等方面。

参考文献 ​

  1. Self-replicative RNA vaccines elicit protection against influenza A virus, respiratory syncytial virus, and a tickborne encephalitis virus. - M N Fleeton;M Chen;P Berglund;G Rhodes;S E Parker;M Murphy;G J Atkins;P Liljeström - The Journal of infectious diseases (2001)
  2. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. - L Alexopoulou;A C Holt;R Medzhitov;R A Flavell - Nature (2001)
  3. Kunjin virus replicon vaccine vectors induce protective CD8+ T-cell immunity. - Itaru Anraku;Tracey J Harvey;Richard Linedale;Joy Gardner;David Harrich;Andreas Suhrbier;Alexander A Khromykh - Journal of virology (2002)
  4. Kunjin virus replicon vectors for human immunodeficiency virus vaccine development. - Tracey J Harvey;Itaru Anraku;Richard Linedale;David Harrich;Jason Mackenzie;Andreas Suhrbier;Alexander A Khromykh - Journal of virology (2003)
  5. mRNA is an endogenous ligand for Toll-like receptor 3. - Katalin Karikó;Houping Ni;John Capodici;Marc Lamphier;Drew Weissman - The Journal of biological chemistry (2004)
  6. Recognition of mRNA cap structures by viral and cellular proteins. - Pierre Fechter;George G Brownlee - The Journal of general virology (2005)
  7. The yin and yang of type I interferon activity in bacterial infection. - Thomas Decker;Mathias Müller;Silvia Stockinger - Nature reviews. Immunology (2005)
  8. Efficient stimulation of HIV-1-specific T cells using dendritic cells electroporated with mRNA encoding autologous HIV-1 Gag and Env proteins. - Ellen R A Van Gulck;Peter Ponsaerts;Leo Heyndrickx;Katleen Vereecken;Filip Moerman;Ann De Roo;Robert Colebunders;Glenn Van den Bosch;Dirk R Van Bockstaele;Viggo F I Van Tendeloo;Sabine Allard;Bernard Verrier;Concepción Marañón;Guillaume Hoeffel;Anne Hosmalin;Zwi N Berneman;Guido Vanham - Blood (2006)
  9. Humoral and cellular immune response to RNA immunization with flavivirus replicons derived from tick-borne encephalitis virus. - Judith H Aberle;Stephan W Aberle;Regina M Kofler;Christian W Mandl - Journal of virology (2005)
  10. High guanine and cytosine content increases mRNA levels in mammalian cells. - Grzegorz Kudla;Leszek Lipinski;Fanny Caffin;Aleksandra Helwak;Maciej Zylicz - PLoS biology (2006)

引用本文的文献 ​

  1. Innovative Mucosal Vaccine Formulations Against Influenza A Virus Infections. - Cynthia Calzas;Christophe Chevalier - Frontiers in immunology (2019)
  2. Advances in Vaccines. - Helen H Mao;Shoubai Chao - Advances in biochemical engineering/biotechnology (2020)
  3. Immunological Analysis of a CCHFV mRNA Vaccine Candidate in Mouse Models. - Touraj Aligholipour Farzani;Katalin Földes;Koray Ergünay;Hakan Gurdal;Aliye Bastug;Aykut Ozkul - Vaccines (2019)
  4. Enlisting the mRNA Vaccine Platform to Combat Parasitic Infections. - Leroy Versteeg;Mashal M Almutairi;Peter J Hotez;Jeroen Pollet - Vaccines (2019)
  5. Establishing Preferred Product Characterization for the Evaluation of RNA Vaccine Antigens. - Cristina Poveda;Amadeo B Biter;Maria Elena Bottazzi;Ulrich Strych - Vaccines (2019)
  6. Advances in RNA Vaccines for Preventive Indications: A Case Study of A Vaccine Against Rabies. - Nicole Armbruster;Edith Jasny;Benjamin Petsch - Vaccines (2019)
  7. Development of Universal Influenza Vaccines Targeting Conserved Viral Proteins. - Seyed Davoud Jazayeri;Chit Laa Poh - Vaccines (2019)
  8. The Rocky Road From Fed-Batch to Continuous Processing With E. coli. - Julian Kopp;Christoph Slouka;Oliver Spadiut;Christoph Herwig - Frontiers in bioengineering and biotechnology (2019)
  9. Comparison of DNA and mRNA vaccines against cancer. - Zohreh Jahanafrooz;Behzad Baradaran;Jafar Mosafer;Mahmoud Hashemzaei;Tayebeh Rezaei;Ahad Mokhtarzadeh;Michael R Hamblin - Drug discovery today (2020)
  10. Protective or Detrimental? Understanding the Role of Host Immunity in Leishmaniasis. - Camila Dos Santos Meira;Lashitew Gedamu - Microorganisms (2019)

... (343 更多 篇文献)

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