Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses.
Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses.
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DOI：
10.1016/j.immuni.2021.11.001
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发表时间：
2021-12-14
期刊：
影响因子：
32.4
通讯作者：
Pardi N
中科院分区：
文献类型：
--
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
佐剂对于提高疫苗接种的适应性免疫反应的质量和强度至关重要。脂质纳米颗粒（LNP）包封核苷修饰mRNA疫苗对严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）具有良好的免疫效果，但该疫苗平台的作用机制尚不清楚。使用流感病毒和SARS-CoV-2 mRNA和蛋白质亚单位疫苗，我们证明了LNP配方具有内在的佐剂活性，可促进诱导强T滤泡辅助细胞、生长期中心B细胞、长寿命浆细胞和记忆B细胞反应，这些反应与小鼠的持久和保护性抗体相关。对比实验表明，该LNP制剂优于广泛使用的mf59样佐剂AddaVax。LNP的佐剂活性依赖于电离脂质成分和IL-6细胞因子诱导，而不是依赖于MyD88或mavs对LNP的感知。我们的研究发现LNPs是一种多功能佐剂，可以增强传统和下一代疫苗平台的功效。核苷修饰mRNA-LNP疫苗的作用机制尚不清楚。Alameh等人证明LNPs在小鼠mRNA和蛋白质亚单位疫苗中具有佐剂活性，可促进Tfh细胞、B细胞和体液反应的诱导。IL-6诱导和可电离脂质成分对LNPs的佐剂活性至关重要。
Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized. Using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines, we demonstrated that our LNP formulation has intrinsic adjuvant activity that promotes induction of strong T follicular helper cell, germinal center B cell, long-lived plasma cell, and memory B cell responses that are associated with durable and protective antibodies in mice. Comparative experiments demonstrated that this LNP formulation outperformed a widely used MF59-like adjuvant, AddaVax. The adjuvant activity of the LNP relies on the ionizable lipid component and on IL-6 cytokine induction but not on MyD88- or MAVS-dependent sensing of LNPs. Our study identified LNPs as a versatile adjuvant that enhances the efficacy of traditional and next-generation vaccine platforms. The mechanism of action of nucleoside-modified mRNA-LNP vaccines is unknown. Alameh et al. demonstrate that LNPs can possess adjuvant activity and promote robust induction of Tfh cell, B cell, and humoral responses when utilized in mRNA and protein subunit vaccines in mice. IL-6 induction and the ionizable lipid component are critical for the adjuvant activity of LNPs.
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