Huis In 't Veld Lisa Gm, Cornelissen Lenneke Am, van den Bogaard Lune, Ansems Marleen, Ho Nataschja I, Adema Gosse J
Radiotherapy and OncoImmunology Laboratory, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
NPJ Vaccines. 2025 Jan 22;10(1):15. doi: 10.1038/s41541-024-01056-y.
Saponin-based adjuvants (SBAs) distinguish themselves as vaccine adjuvants by instigating a potent activation of CD8+ T cells. Previously, we discovered SBA's ability to induce cross-presentation in dendritic cells (DCs) leading to CD8+ T cell activation. Moreover, the MHCIICD11b bone marrow-derived DC (BMDC) subset was identified to be the most responsive DC subset to SBA treatment. To further investigate SBA's mode of action, labeling of SBAs was optimized with the fluorescent dye SP-DiIC(3). Efficient uptake of SBAs occurs specifically by MHCIICD11b BMDCs and bone marrow-derived macrophages (BMDMs) in vitro and cDC2s and macrophages ex vivo. Furthermore, SBAs are primarily taken up by clathrin-mediated endocytosis and uptake induces lipid bodies and antigen translocation to the cytosol in MHCIICD11b BMDCs and BMDMs. Importantly, BMDMs treated with SBAs exhibit cross-presentation leading to potent CD8+ T cells activation. Our findings explain the potency of SBAs as vaccine adjuvants and contribute to vaccine development.
基于皂苷的佐剂（SBA）通过强烈激活CD8+ T细胞，使其在疫苗佐剂中脱颖而出。此前，我们发现SBA能够在树突状细胞（DC）中诱导交叉呈递，从而导致CD8+ T细胞活化。此外，MHCII+CD11b骨髓来源的DC（BMDC）亚群被确定为对SBA处理反应最灵敏的DC亚群。为了进一步研究SBA的作用模式，我们用荧光染料SP-DiIC(3)对SBA进行了优化标记。在体外，MHCII+CD11b BMDC和骨髓来源的巨噬细胞（BMDM）能够特异性地高效摄取SBA，在体内，cDC2和巨噬细胞也能摄取。此外，SBA主要通过网格蛋白介导的内吞作用被摄取，摄取会诱导MHCII+CD11b BMDC和BMDM中脂滴的形成以及抗原向细胞质的转运。重要的是，用SBA处理的BMDM表现出交叉呈递，从而导致强大的CD8+ T细胞活化。我们的研究结果解释了SBA作为疫苗佐剂的效力，并为疫苗开发做出了贡献。
