mRNA vaccines manufacturing: Challenges and bottlenecks.

文献信息

DOI	10.1016/j.vaccine.2021.03.038
PMID	33771389
期刊	Vaccine
影响因子	3.5
JCR 分区	Q2
发表年份	2021
被引次数	205
关键词	疫苗接种, mRNA 应用, mRNA 生产, mRNA 疫苗
文献类型	Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN	0264-410X
页码	2190-2200
期号	39(16)
作者	Sara Sousa Rosa, Duarte M F Prazeres, Ana M Azevedo, Marco P C Marques

一句话小结

本研究综述了mRNA疫苗在公共卫生中的重要性，强调其作为传统疫苗替代选择的潜力，尤其是在新冠疫情中的成功应用。作者探讨了mRNA疫苗大规模生产面临的挑战与瓶颈，指出需建立高效且经济的生产流程，以应对未来的健康危机。

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疫苗接种 · mRNA 应用 · mRNA 生产 · mRNA 疫苗

摘要

疫苗是公共卫生中最重要的工具之一，在传染病控制中发挥着重要作用。由于其精准、安全的特性以及灵活的生产能力，mRNA疫苗正逐渐成为传统疫苗的新替代选择。实际上，mRNA疫苗是许多公司应对新冠疫情时的首选技术，也是首个在美国和欧洲联盟获得批准作为预防性治疗的技术。此外，mRNA疫苗正在临床上研究用于治疗多种疾病，包括癌症、艾滋病、流感甚至遗传性疾病。对mRNA疫苗的需求增加需要一个技术平台和具有成本效益的生产过程，并且需要对产品特性进行明确的定义。mRNA疫苗的大规模生产包括1到2步的体外反应，随后是一个多步骤的纯化平台，可能包括Dnase消化、沉淀、色谱或切向流过滤。在这篇综述中，我们描述了mRNA疫苗的最新进展，重点关注需要解决的制造挑战和瓶颈，以将这一新疫苗技术转化为应对新兴健康危机的有效、快速和经济的解决方案。

英文摘要

Vaccines are one of the most important tools in public health and play an important role in infectious diseases control. Owing to its precision, safe profile and flexible manufacturing, mRNA vaccines are reaching the stoplight as a new alternative to conventional vaccines. In fact, mRNA vaccines were the technology of choice for many companies to combat the Covid-19 pandemic, and it was the first technology to be approved in both United States and in Europe Union as a prophylactic treatment. Additionally, mRNA vaccines are being studied in the clinic to treat a number of diseases including cancer, HIV, influenza and even genetic disorders. The increased demand for mRNA vaccines requires a technology platform and cost-effective manufacturing process with a well-defined product characterisation. Large scale production of mRNA vaccines consists in a 1 or 2-step in vitro reaction followed by a purification platform with multiple steps that can include Dnase digestion, precipitation, chromatography or tangential flow filtration. In this review we describe the current state-of-art of mRNA vaccines, focusing on the challenges and bottlenecks of manufacturing that need to be addressed to turn this new vaccination technology into an effective, fast and cost-effective response to emerging health crises.

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主要研究问题

核心洞察

研究背景和目的

mRNA疫苗因其精准、安全和灵活的生产能力，成为公共卫生的重要工具，尤其在应对新冠疫情中表现突出。尽管现有疫苗技术有效，但传统疫苗的生产过程漫长且成本高，急需开发新的疫苗技术以提高应对疫情的能力。本文旨在总结mRNA疫苗的制造挑战与瓶颈，并探讨其在疫苗开发中的应用前景。

主要方法/材料/实验设计

本研究回顾了mRNA疫苗的生产过程，包括上游和下游的各个环节，强调了mRNA的结构及其交付方式。生产过程分为以下几个步骤：

上游处理：通过体外转录反应生成mRNA。
纯化：包括DNase消化、沉淀、色谱法和切向流过滤等步骤，以去除杂质。
LNP封装：将纯化后的mRNA与脂质纳米颗粒结合，提升稳定性和细胞摄取效率。
填充与完成：最终产品的制备和包装。

关键结果和发现

mRNA疫苗具有较高的安全性和灵活性，能够迅速应对新出现的健康危机。
生产过程中，虽然体外转录反应快速且安全，但仍面临材料成本高、下游纯化步骤复杂等挑战。
mRNA疫苗在多种疾病（如癌症、HIV和流感）中显示出良好的临床应用潜力，尤其在新冠疫苗的开发中取得了显著成就。

主要结论/意义/创新性

mRNA疫苗代表了疫苗技术的一个重大突破，具备快速响应公共卫生危机的潜力。其制造过程的简化和标准化可以显著降低生产成本，提高疫苗的可及性。随着技术的进步，mRNA疫苗有望在更多疾病的预防和治疗中发挥作用。

研究局限性和未来方向

当前mRNA疫苗的生产仍依赖于高成本的原材料和复杂的下游处理过程，限制了其广泛应用。
未来的研究应集中在开发更高效、低成本的连续生产流程，以及优化纯化步骤，以提升mRNA疫苗的市场竞争力。
随着临床试验的不断推进，mRNA疫苗的应用范围将进一步扩展，包括其他传染病和癌症的治疗。

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... (195 更多篇文献)

mRNA vaccines manufacturing: Challenges and bottlenecks. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

研究背景和目的 ​

主要方法/材料/实验设计 ​

关键结果和发现 ​

主要结论/意义/创新性 ​

研究局限性和未来方向 ​

参考文献 ​

引用本文的文献 ​