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Curr Top Microbiol Immunol. 2022;440:31-70. doi: 10.1007/82_2021_233.
Self-amplifying mRNAs derived from the genomes of positive-strand RNA viruses have recently come into focus as a promising technology platform for vaccine development. Non-virally delivered self-amplifying mRNA vaccines have the potential to be highly versatile, potent, streamlined, scalable, and inexpensive. By amplifying their genome and the antigen encoding mRNA in the host cell, the self-amplifying mRNA mimics a viral infection, resulting in sustained levels of the target protein combined with self-adjuvanting innate immune responses, ultimately leading to potent and long-lasting antigen-specific humoral and cellular immune responses. Moreover, in principle, any eukaryotic sequence could be encoded by self-amplifying mRNA without the need to change the manufacturing process, thereby enabling a much faster and flexible research and development timeline than the current vaccines and hence a quicker response to emerging infectious diseases. This chapter highlights the rapid progress made in using non-virally delivered self-amplifying mRNA-based vaccines against infectious diseases in animal models. We provide an overview of the unique attributes of this vaccine approach, summarize the growing body of work defining its mechanism of action, discuss the current challenges and latest advances, and highlight perspectives about the future of this promising technology.
最近，正链 RNA 病毒基因组衍生的自我扩增 mRNA 作为疫苗开发的一种有前途的技术平台受到了关注。非病毒递送的自我扩增 mRNA 疫苗具有高度多功能性、高效性、简化性、可扩展性和低成本的潜力。通过在宿主细胞中扩增其基因组和编码抗原的 mRNA，自我扩增 mRNA 模拟病毒感染，导致目标蛋白的持续水平与自我佐剂固有免疫反应相结合，最终导致有效的、持久的抗原特异性体液和细胞免疫反应。此外，原则上，任何真核序列都可以通过自我扩增 mRNA 进行编码，而无需改变制造工艺，从而使研究和开发的时间线比当前的疫苗更快、更灵活，从而能够更快地应对新出现的传染病。本章重点介绍了在动物模型中使用非病毒递送的自我扩增基于 mRNA 的疫苗来对抗传染病方面取得的快速进展。我们概述了这种疫苗方法的独特属性，总结了越来越多的关于其作用机制的工作，讨论了当前的挑战和最新进展，并强调了该有前途的技术的未来前景。
