Ghent Research Group on Nanomedicines, Faculty of Pharmacy, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Department of Biochemistry and Molecular Biology, University of British Columbia, BC V6T 1Z4, Vancouver, Canada.
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Immunity. 2022 Nov 8;55(11):1993-2005. doi: 10.1016/j.immuni.2022.10.014.
The lipid nanoparticle (LNP)-encapsulated, nucleoside-modified mRNA platform has been used to generate safe and effective vaccines in record time against COVID-19. Here, we review the current understanding of the manner whereby mRNA vaccines induce innate immune activation and how this contributes to protective immunity. We discuss innate immune sensing of mRNA vaccines at the cellular and intracellular levels and consider the contribution of both the mRNA and the LNP components to their immunogenicity. A key message that is emerging from recent observations is that the LNP carrier acts as a powerful adjuvant for this novel vaccine platform. In this context, we highlight important gaps in understanding and discuss how new insight into the mechanisms underlying the effectiveness of mRNA-LNP vaccines may enable tailoring mRNA and carrier molecules to develop vaccines with greater effectiveness and milder adverse events in the future.
脂质纳米颗粒（LNP）包裹的核苷修饰 mRNA 平台已被用于在创纪录的时间内针对 COVID-19 生成安全有效的疫苗。在这里，我们回顾了目前对 mRNA 疫苗如何诱导先天免疫激活以及这如何有助于保护性免疫的理解。我们讨论了细胞内和细胞内水平上 mRNA 疫苗的先天免疫感应，并考虑了 mRNA 和 LNP 成分对其免疫原性的贡献。最近的观察结果中出现的一个关键信息是，LNP 载体是这种新型疫苗平台的强大佐剂。在这种情况下，我们强调了理解中的重要差距，并讨论了对 mRNA-LNP 疫苗有效性背后机制的新认识如何能够使未来开发具有更高效力和更轻微不良反应的疫苗的 mRNA 和载体分子。
