Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nat Rev Drug Discov. 2024 Nov;23(11):838-861. doi: 10.1038/s41573-024-01042-y. Epub 2024 Oct 4.
The concept of mRNA-based vaccines emerged more than three decades ago. Groundbreaking discoveries and technological advancements over the past 20 years have resolved the major roadblocks that initially delayed application of this new vaccine modality. The rapid development of nucleoside-modified COVID-19 mRNA vaccines demonstrated that this immunization platform is easy to develop, has an acceptable safety profile and can be produced at a large scale. The flexibility and ease of antigen design have enabled mRNA vaccines to enter development for a wide range of viruses as well as for various bacteria and parasites. However, gaps in our knowledge limit the development of next-generation mRNA vaccines with increased potency and safety. A deeper understanding of the mechanisms of action of mRNA vaccines, application of novel technologies enabling rational antigen design, and innovative vaccine delivery strategies and vaccination regimens will likely yield potent novel vaccines against a wide range of pathogens.
mRNA 疫苗的概念早在三十多年前就已经出现。过去 20 年来，突破性的发现和技术进步解决了最初阻碍这种新型疫苗模式应用的主要障碍。核苷修饰的 COVID-19 mRNA 疫苗的快速发展表明，这种免疫平台易于开发，具有可接受的安全性，并可大规模生产。抗原设计的灵活性和简便性使 mRNA 疫苗能够针对广泛的病毒以及各种细菌和寄生虫进行开发。然而，我们知识上的差距限制了具有更高效力和安全性的下一代 mRNA 疫苗的发展。更深入地了解 mRNA 疫苗的作用机制、应用能够实现合理抗原设计的新技术，以及创新的疫苗输送策略和接种方案，可能会针对广泛的病原体产生有效的新型疫苗。
