Innate immune mechanisms of mRNA vaccines.
Innate immune mechanisms of mRNA vaccines.
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DOI：
10.1016/j.immuni.2022.10.014
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发表时间：
2022-11-08
期刊：
影响因子：
32.4
通讯作者：
Pardi, Norbert
中科院分区：
文献类型：
--
作者：
Verbeke, Rein;Hogan, Michael J.;Lore, Karin;Pardi, Norbert
脂质纳米颗粒（LNP）封装的核苷修饰的mRNA平台已用于在创纪录的时间内生产安全有效的COVID-19疫苗。在这里，我们回顾了目前的理解，mRNA疫苗诱导先天免疫激活的方式，以及如何这有助于保护性免疫。我们讨论了先天性免疫传感的mRNA疫苗在细胞和细胞内水平，并考虑的mRNA和LNP组件的贡献，其免疫原性。从最近的观察中出现的一个关键信息是，LNP载体作为这种新型疫苗平台的强大佐剂。在这种情况下，我们强调了理解的重要差距，并讨论了对mRNA-LNP疫苗有效性机制的新见解如何能够定制mRNA和载体分子，以开发未来具有更高有效性和更温和不良事件的疫苗。脂质纳米颗粒封装的核苷修饰的mRNA疫苗产生针对COVID-19的适应性免疫应答。在这里，Pardi及其同事回顾了这种疫苗形式的先天免疫传感途径，并讨论了可能产生下一代具有改善的免疫原性和降低的反应原性的mRNA疫苗的研究方向。
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. Lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccines produce adaptive immune responses protective against COVID-19. Here, Pardi and colleagues review the innate immune-sensing pathways of this vaccine modality and discuss research directions that may yield a next generation of mRNA vaccines with improved immunogenicity and reduced reactogenicity.
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影响因子：
32.4
作者：
Alameh MG;Tombácz I;Bettini E;Lederer K;Sittplangkoon C;Wilmore JR;Gaudette BT;Soliman OY;Pine M;Hicks P;Manzoni TB;Knox JJ;Johnson JL;Laczkó D;Muramatsu H;Davis B;Meng W;Rosenfeld AM;Strohmeier S;Lin PJC;Mui BL;Tam YK;Karikó K;Jacquet A;Krammer F;Bates P;Cancro MP;Weissman D;Luning Prak ET;Allman D;Locci M;Pardi N
通讯作者：
Pardi N
影响因子：
6.4
作者：
Durbin AF;Wang C;Marcotrigiano J;Gehrke L
通讯作者：
Gehrke L
影响因子：
5.9
作者：
Carrasco MJ;Alishetty S;Alameh MG;Said H;Wright L;Paige M;Soliman O;Weissman D;Cleveland TE 4th;Grishaev A;Buschmann MD
通讯作者：
Buschmann MD
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
DOI：
10.1073/pnas.2109256118
发表时间：
2021-12-28
影响因子：
11.1
作者：
Dilliard, Sean A.;Cheng, Qiang;Siegwart, Daniel J.
通讯作者：
Siegwart, Daniel J.