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A Comprehensive Review of mRNA Vaccines.

文献信息

DOI10.3390/ijms24032700
PMID36769023
期刊International journal of molecular sciences
影响因子4.9
JCR 分区Q1
发表年份2023
被引次数152
关键词聚乙二醇化脂质, 接受, 佐剂, 抗原呈递, 阳离子脂质
文献类型Journal Article, Review
ISSN1422-0067
期号24(3)
作者Vrinda Gote, Pradeep Kumar Bolla, Nagavendra Kommineni, Arun Butreddy, Pavan Kumar Nukala, Sushesh Srivatsa Palakurthi, Wahid Khan

一句话小结

本综述探讨了mRNA疫苗的发展历程及其作为COVID-19疫苗的优势,重点分析了mRNA的结构、免疫功能、脂质纳米颗粒的应用以及生产过程。文章还展望了mRNA疫苗的未来,包括冻干技术和改善递送系统的潜力,强调了纳米技术在疫苗递送中的重要性。

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聚乙二醇化脂质 · 接受 · 佐剂 · 抗原呈递 · 阳离子脂质

摘要

mRNA疫苗因其高效性、安全性和有效性、快速临床开发的能力以及潜在的低成本快速生产,已被证明是传统疫苗的有力替代品。这些疫苗从最初的好奇对象发展为COVID-19大流行疫苗的领跑者。纳米技术在mRNA疫苗递送载体开发领域的进展具有重要意义。在本综述中,我们总结了mRNA疫苗的各个方面。文章描述了mRNA的结构、其免疫诱导的药理功能、脂质纳米颗粒(LNPs)以及mRNA疫苗生产的上游、下游和配方过程。此外,临床试验中的mRNA疫苗也得到了描述。我们还深入探讨了mRNA疫苗的未来展望,包括冻干技术、递送系统,以及LNPs对抗原呈递细胞和树突状细胞的靶向等内容。

英文摘要

mRNA vaccines have been demonstrated as a powerful alternative to traditional conventional vaccines because of their high potency, safety and efficacy, capacity for rapid clinical development, and potential for rapid, low-cost manufacturing. These vaccines have progressed from being a mere curiosity to emerging as COVID-19 pandemic vaccine front-runners. The advancements in the field of nanotechnology for developing delivery vehicles for mRNA vaccines are highly significant. In this review we have summarized each and every aspect of the mRNA vaccine. The article describes the mRNA structure, its pharmacological function of immunity induction, lipid nanoparticles (LNPs), and the upstream, downstream, and formulation process of mRNA vaccine manufacturing. Additionally, mRNA vaccines in clinical trials are also described. A deep dive into the future perspectives of mRNA vaccines, such as its freeze-drying, delivery systems, and LNPs targeting antigen-presenting cells and dendritic cells, are also summarized.

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主要研究问题

  1. mRNA疫苗在临床试验中的表现如何,与传统疫苗相比有什么优势?
  2. 纳米技术在mRNA疫苗递送系统中的具体应用有哪些,如何提高疫苗的效果?
  3. 未来mRNA疫苗的发展方向是什么,特别是在冷冻干燥和抗原呈递细胞靶向方面?
  4. 在mRNA疫苗的生产过程中,如何优化上游和下游的制造流程以降低成本?
  5. mRNA疫苗的安全性和副作用研究现状如何,针对不同人群的反应是否存在差异?

核心洞察

研究背景和目的

mRNA疫苗因其高效、安全和快速开发的潜力,成为传统疫苗的有力替代品。特别是在COVID-19大流行期间,mRNA疫苗如Pfizer-BioNTech和Moderna疫苗迅速获得批准并广泛应用。本综述旨在全面总结mRNA疫苗的结构、免疫机制、制造过程、临床试验及未来发展方向。

主要方法/材料/实验设计

本研究采用文献综述的方法,系统分析了mRNA疫苗的各个方面,包括mRNA的结构特征、免疫反应的药理学、脂质纳米颗粒(LNPs)的作用以及mRNA疫苗的生产流程。

Mermaid diagram

关键结果和发现

  1. mRNA结构:包括5'帽、3'非翻译区(UTR)和Poly(A)尾,这些结构对于mRNA的稳定性和翻译效率至关重要。
  2. 免疫反应机制:mRNA疫苗通过转染肌肉细胞和抗原呈递细胞(APCs),引发细胞免疫和体液免疫反应。
  3. LNPs的作用:脂质纳米颗粒作为mRNA的递送载体,能够保护mRNA免受降解,提高其生物利用度。
  4. 生产流程:包括上游生产(IVT反应)、下游纯化(如SEC和IEC)和最终配方(LNP形成)。

主要结论/意义/创新性

mRNA疫苗代表了疫苗开发的重大进展,特别是在应对传染病方面的应用。其快速的开发周期和有效的免疫反应使其在公共卫生领域具有重要意义。此外,LNPs的使用大大提高了mRNA疫苗的递送效率和稳定性,为未来的疫苗研发提供了新的思路。

研究局限性和未来方向

尽管mRNA疫苗显示出良好的安全性和有效性,但仍存在一些挑战,包括:

  • 抗体反应的持续时间:需进一步研究以了解不同抗原的免疫持久性。
  • 安全性问题:部分疫苗在临床试验中出现过敏反应,需要优化成分。
  • 疫苗接受度:公众对疫苗的接受程度影响接种率,需加强科普宣传。

未来的研究方向包括开发稳定性更高的疫苗,优化递送系统,以及针对特定人群(如老年人和孕妇)的疫苗研发。

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  3. Recent Advancement in mRNA Vaccine Development and Applications. - Nojoud Al Fayez;Majed S Nassar;Abdullah A Alshehri;Meshal K Alnefaie;Fahad A Almughem;Bayan Y Alshehri;Abdullah O Alawad;Essam A Tawfik - Pharmaceutics (2023)
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  10. mRNA-based VP8* nanoparticle vaccines against rotavirus are highly immunogenic in rodents. - Sandro Roier;Vidya Mangala Prasad;Monica M McNeal;Kelly K Lee;Benjamin Petsch;Susanne Rauch - NPJ vaccines (2023)

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