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Nanomaterial Delivery Systems for mRNA Vaccines.

文献信息

DOI10.3390/vaccines9010065
PMID33478109
期刊Vaccines
影响因子3.4
JCR 分区Q2
发表年份2021
被引次数229
关键词SARS-CoV-2, 离子化脂质, 脂质纳米颗粒, mRNA, 疫苗
文献类型Journal Article, Review
ISSN2076-393X
期号9(1)
作者Michael D Buschmann, Manuel J Carrasco, Suman Alishetty, Mikell Paige, Mohamad Gabriel Alameh, Drew Weissman

一句话小结

近年来,mRNA疫苗在SARS-CoV-2的临床试验中取得成功,部分得益于脂质纳米颗粒递送系统的创新,这些系统不仅有效促进mRNA的表达,还增强了疫苗的免疫反应。本文综述了mRNA递送系统的现状及其在疫苗开发中的关键作用,强调了脂质纳米颗粒在疫苗效果中的重要性。

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SARS-CoV-2 · 离子化脂质 · 脂质纳米颗粒 · mRNA · 疫苗

摘要

近年来,mRNA疫苗在SARS-CoV-2临床试验中的成功,部分归功于脂质纳米颗粒递送系统的开发。这些系统不仅能够在肌肉注射后高效表达mRNA编码的免疫原,还在作为佐剂和疫苗反应性方面发挥作用。我们将对mRNA递送系统进行概述,随后重点介绍目前SARS-CoV-2疫苗临床试验中使用的脂质纳米颗粒。最后,本综述将分析脂质纳米颗粒在mRNA疫苗中表现的决定因素。

英文摘要

The recent success of mRNA vaccines in SARS-CoV-2 clinical trials is in part due to the development of lipid nanoparticle delivery systems that not only efficiently express the mRNA-encoded immunogen after intramuscular injection, but also play roles as adjuvants and in vaccine reactogenicity. We present an overview of mRNA delivery systems and then focus on the lipid nanoparticles used in the current SARS-CoV-2 vaccine clinical trials. The review concludes with an analysis of the determinants of the performance of lipid nanoparticles in mRNA vaccines.

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主要研究问题

  1. 除了脂质纳米颗粒,还有哪些纳米材料可以用于mRNA疫苗的递送系统?
  2. 脂质纳米颗粒在不同类型的mRNA疫苗中表现出的效果有何差异?
  3. 如何优化脂质纳米颗粒的组成以提高mRNA疫苗的免疫反应?
  4. 在mRNA疫苗的临床试验中,脂质纳米颗粒的反应性和副作用如何影响疫苗的接受度?
  5. 有哪些新兴技术可以改善纳米材料在mRNA疫苗中的应用效果?

核心洞察

研究背景和目的

mRNA疫苗在COVID-19大流行中获得了显著关注,尤其是BioNTech/Pfizer和Moderna等公司的疫苗在临床试验中表现出超过94%的有效性。这一成功部分归功于脂质纳米颗粒(LNP)递送系统的开发,这些系统不仅有效地传递mRNA,还充当了佐剂,影响疫苗的反应性。本文旨在概述mRNA递送系统的发展,并总结SARS-CoV-2 mRNA疫苗的前临床和临床研究结果,分析递送系统的特性如何促进其成功。

主要方法/材料/实验设计

本研究采用文献综述的方法,系统性分析了当前用于mRNA疫苗的递送系统,尤其是脂质纳米颗粒的设计与优化。以下是技术路线的Mermaid代码:

Mermaid diagram

关键结果和发现

  1. 脂质纳米颗粒的组成:现代mRNA疫苗的LNP通常由离子脂质、磷脂、胆固醇和PEG脂质组成,设计的关键在于优化离子脂质的pKa,以增强细胞内的mRNA释放。
  2. 临床试验结果:BioNTech/Pfizer的BNT162b2和Moderna的mRNA-1273疫苗在不同人群中均显示出高效的免疫应答,且较低的剂量(如30µg和100µg)均能产生强烈的中和抗体反应。
  3. 递送效率:研究表明,使用LNP递送的mRNA相比裸mRNA的细胞摄取率提高了1000倍,且LNP具有自身的免疫增强特性,能够促进T细胞和B细胞的活化。

主要结论/意义/创新性

本综述强调了脂质纳米颗粒在mRNA疫苗递送中的关键作用,揭示了其在疫苗有效性和安全性中的双重功能。通过对LNP的设计优化,能够显著提高疫苗的免疫原性,推动mRNA技术在其他疾病预防和治疗中的应用。

研究局限性和未来方向

  1. 局限性:当前研究主要集中在SARS-CoV-2疫苗的LNP,其他疾病的mRNA疫苗研究相对较少,且不同类型的LNP在临床试验中的表现可能存在差异。
  2. 未来方向:未来研究应集中在改进LNP的设计,以提高递送效率,降低免疫原性,同时探索其他递送系统(如聚合物和纳米颗粒)在mRNA疫苗中的应用。此外,评估不同年龄和健康状态人群对mRNA疫苗的反应差异也是重要的研究方向。

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引用本文的文献

  1. Synthetic Messenger RNA-Based Vaccines: from Scorn to Hype. - Steve Pascolo - Viruses (2021)
  2. Nanomaterials Synthesis through Microfluidic Methods: An Updated Overview. - Adelina-Gabriela Niculescu;Cristina Chircov;Alexandra Cătălina Bîrcă;Alexandru Mihai Grumezescu - Nanomaterials (Basel, Switzerland) (2021)
  3. Role of nanotechnology behind the success of mRNA vaccines for COVID-19. - Amit Khurana;Prince Allawadhi;Isha Khurana;Sachin Allwadhi;Ralf Weiskirchen;Anil Kumar Banothu;Deepak Chhabra;Kamaldeep Joshi;Kala Kumar Bharani - Nano today (2021)
  4. mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability. - Linde Schoenmaker;Dominik Witzigmann;Jayesh A Kulkarni;Rein Verbeke;Gideon Kersten;Wim Jiskoot;Daan J A Crommelin - International journal of pharmaceutics (2021)
  5. mRNA-Based Vaccines. - Frank Kowalzik;Daniel Schreiner;Christian Jensen;Daniel Teschner;Stephan Gehring;Fred Zepp - Vaccines (2021)
  6. Insights into Antibody-Mediated Alphavirus Immunity and Vaccine Development Landscape. - Anthony Torres-Ruesta;Rhonda Sin-Ling Chee;Lisa F P Ng - Microorganisms (2021)
  7. An Updated Review of SARS-CoV-2 Vaccines and the Importance of Effective Vaccination Programs in Pandemic Times. - Cielo García-Montero;Oscar Fraile-Martínez;Coral Bravo;Diego Torres-Carranza;Lara Sanchez-Trujillo;Ana M Gómez-Lahoz;Luis G Guijarro;Natalio García-Honduvilla;Angel Asúnsolo;Julia Bujan;Jorge Monserrat;Encarnación Serrano;Melchor Álvarez-Mon;Juan A De León-Luis;Miguel A Álvarez-Mon;Miguel A Ortega - Vaccines (2021)
  8. Novel Vaccine Technologies in Veterinary Medicine: A Herald to Human Medicine Vaccines. - Virginia Aida;Vasilis C Pliasas;Peter J Neasham;J Fletcher North;Kirklin L McWhorter;Sheniqua R Glover;Constantinos S Kyriakis - Frontiers in veterinary science (2021)
  9. Multifunctional Immunoadjuvants for Use in Minimalist Nucleic Acid Vaccines. - Saed Abbasi;Satoshi Uchida - Pharmaceutics (2021)
  10. mRNA Innovates the Vaccine Field. - Norbert Pardi - Vaccines (2021)

... (219 更多 篇文献)


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