mRNA疫苗：战胜新型冠状病毒感染的重要突破

2023年诺贝尔生理学或医学奖授予医学家卡塔琳·卡里科（Katalin Karikó）和德鲁·韦斯曼（Drew Weissman），以表彰他们在核苷碱基修饰方面的发现，这些修饰的发现对于开发针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的有效mRNA疫苗至关重要。疫苗接种是预防感染性疾病最经济最有效的措施。到目前为止，疫苗已经从灭活疫苗、重组蛋白疫苗进入到了第三代核酸疫苗。两位科学家的研究发现，掺入修饰碱基的体外转录mRNA可以逃避不良的免疫激活，解决了体外转录的mRNA过度引起炎症反应的问题；进一步的研究发现，含假尿苷的mRNA能更有效地进行翻译。同时 德鲁·韦斯曼对于递送系统的研究与发展也做出了重要贡献。新型冠状病毒感染（COVID-19）爆发后，以两位科学家的研究为基础，mRNA疫苗的研发技术体系被完善，在COVID-19疫情期间为人类抗击SARS-CoV-2起到非常重要的作用。本文介绍了疫苗发展的过程、mRNA疫苗中重要的核苷酸修饰和脂质纳米颗粒技术、针对SARS-CoV-2的mRNA疫苗以及技术发展的总结与展望。

mRNA Vaccine: an Important Breakthrough in Defeating COVID-19

The 2023 Nobel Prize in Physiology or Medicine was awarded to medical scientists Katalin Karikó and Drew Weissman for their discovery of nucleoside base modification. The two researchers found that mRNA produced from modified nucleoside bases can evade innate immune recognition and improve protein expression. The discovery of these modifications is essential for the development of an effective mRNA vaccine against novel coronavirus SARS-CoV-2. Vaccination is the most economical and effective measure to prevent infectious diseases. So far, the vaccine has entered the third generation of nucleic acid vaccine from inactivated vaccine, subunit vaccine and recombinant protein vaccine. mRNA vaccine has the potential of high efficiency, rapid development, low-cost production and safe use. It is not a replication vector, and it does not have the characteristics of antibiotic resistance, genome integration and strong immunogenicity. Furthermore, corresponding mRNA vaccine can be quickly produced for different strains in large-scale, which speeds up the production process. However, mRNA synthesized in vitro is the ligand of Toll-like receptors. Once mRNA synthesized in vitro activates these receptors, the innate immune responses in the body will be turned on and a large amount of type I interferon will be produced, and mRNA will face the risk of degradation. The study of Katalin Karikó and Drew Weissman found that in vitro transcribed mRNA with modified bases can escape poor immune activation and solve the problem of inflammatory response stimulated by in vitro transcribed mRNA. Further studies have found that mRNA containing pseudouridine can be translated more effectively. At the same time, Drew Weissman has made an important contribution to the research and development of delivery system. After the outbreak of COVID-19, based on the research of two scientists, together with the development of efficient delivery systems such as lipid nanoparticles (LNPs) delivery system and one-component ionizable amphiphilic Janus dendrimer delivery system, the stability of SARS-CoV-2 prickle antigen and unparalleled investment by industry and government, the research and development technology system of mRNA vaccine was improved. Two very successful mRNA-based SARS-CoV-2 vaccines were approved at the end of 2020, which played a very important role in fighting COVID-19 during COVID-19 epidemic and paved the way for future mRNA applications. mRNA vaccine also has great potential in inhibiting tumor growth and regenerative medicine. Therefore, the circular RNA vaccine can also be studied. This paper introduces the process of vaccine development, the important nucleotide modification and lipid nanoparticles technology in mRNA vaccine, the in vivo effect of mRNA vaccine and the summary and prospect of technical development.