Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Immunity. 2021 Dec 14;54(12):2877-2892.e7. doi: 10.1016/j.immuni.2021.11.001. Epub 2021 Nov 4.
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.
佐剂对于提高疫苗接种后适应性免疫反应的质量和强度至关重要。脂质纳米颗粒(LNP)包裹的核苷修饰 mRNA 疫苗已被证明对严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)具有强大的功效,但这种疫苗平台的作用机制尚未得到很好的描述。我们使用流感病毒和 SARS-CoV-2 mRNA 和蛋白亚单位疫苗,证明了我们的 LNP 配方具有内在的佐剂活性,可促进强烈的滤泡辅助性 T 细胞、生发中心 B 细胞、长寿浆细胞和记忆 B 细胞的诱导,这些细胞与小鼠中持久和保护性的抗体相关。比较实验表明,这种 LNP 配方优于一种广泛使用的 MF59 样佐剂 AddaVax。LNP 的佐剂活性依赖于可离子化的脂质成分和 IL-6 细胞因子的诱导,而不依赖于 LNP 的 MyD88 或 MAVS 依赖性感应。我们的研究确定 LNP 是一种多功能佐剂,可增强传统和新一代疫苗平台的功效。
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