美国宾夕法尼亚大学Norbert Pardi、Michela Locci等研究人员合作发现，脂质纳米颗粒通过诱导强大的T滤泡辅助细胞和体液反应提高mRNA和蛋白亚基疫苗的功效。相关论文于2021年11月4日在线发表在《免疫》杂志上。

利用流感病毒和SARS-CoV-2 mRNA和蛋白亚基疫苗，研究人员证明了脂质纳米颗粒（LNP）配方具有本质的佐剂活性，可以促进诱导小鼠体内强大的T滤泡辅助细胞、生殖中心B细胞、长寿浆细胞和记忆B细胞反应，并与持久的保护性抗体有关。比较实验表明，这种LNP的性能优于广泛使用的MF59类佐剂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，而不是依赖于MyD88或MAVS对LNP的感应。这项研究发现LNP是一种多功能的佐剂，可以提高传统和下一代疫苗平台的功效。

据介绍，佐剂对于提高疫苗接种的适应性免疫反应的质量和程度至关重要。LNP包裹的核苷修饰的mRNA疫苗对SARS-CoV-2显示出巨大的功效，但这种疫苗平台的作用机制还没有得到很好的描述。

附：英文原文

Title: Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses

Author: Mohamad-Gabriel Alameh, István Tombácz, Emily Bettini, Katlyn Lederer, Chutamath Sittplangkoon, Joel R. Wilmore, Brian T. Gaudette, Ousamah Y. Soliman, Matthew Pine, Philip Hicks, Tomaz B. Manzoni, James J. Knox, John L. Johnson, Dorottya Laczkó, Hiromi Muramatsu, Benjamin Davis, Wenzhao Meng, Aaron M. Rosenfeld, Shirin Strohmeier, Paulo J.C. Lin, Barbara L. Mui, Ying K. Tam, Katalin Karikó, Alain Jacquet, Florian Krammer, Paul Bates, Michael P. Cancro, Drew Weissman, Eline T. Luning Prak, David Allman, Michela Locci, Norbert Pardi

Issue&Volume: 2021-11-04

Abstract: 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 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 the 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 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 both traditional and next-generation vaccine platforms.

DOI: 10.1016/j.immuni.2021.11.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00490-8