一种稳定的纳米颗粒DDA/MMG制剂与CpG ODN 1826协同作用，以增强CD4⁺ T细胞反应。
A stable nanoparticulate DDA/MMG formulation acts synergistically with CpG ODN 1826 to enhance the CD4⁺ T-cell response.
作者信息
Karlsen Kasper, Korsholm Karen Smith, Mortensen Rasmus, Ghiasi Seyed Mojtaba, Andersen Peter, Foged Camilla, Christensen Dennis
机构信息
Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, Copenhagen S, Denmark.
出版信息
Nanomedicine (Lond). 2014 Dec;9(17):2625-38. doi: 10.2217/nnm.14.197.
AIM
To combine the dimethyldioctadecyl ammonium/monomycoloyl glycerol (DDA/MMG) liposomal vaccine adjuvant with the Toll-like receptor (TLR) ligands poly(I:C) (TLR3), flagellin (TLR5) or CpG oligodeoxynucleotide 1826 (TLR9) and investigate their physicochemical properties as well as their CD4(+) T-cell-inducing capacity.
MATERIALS & METHODS: Formulations were investigated by dynamic light scattering and differential scanning calorimetry. Their CD4(+) T-cell induction with a tuberculosis antigen was analyzed by multiplex cytokine analysis, ELISA and intracellular cytokine staining.
RESULTS
DDA/MMG/CpG was the best combination for obtaining increased CD4(+) T-cell responses. However, coformulating CpG and DDA/MMG liposomes led to instability and the formulation was therefore optimized systematically using a design of experiment.
CONCLUSION
The nanoparticulate DDA/MMG/CpG adjuvant can be stabilized and synergistically enhances CD4(+) T-cell responses compared with DDA/MMG liposomes.
目的
将二甲基二十八烷基铵/单霉菌酸甘油酯（DDA/MMG）脂质体疫苗佐剂与Toll样受体（TLR）配体聚肌苷酸:聚胞苷酸（poly(I:C)，TLR3）、鞭毛蛋白（TLR5）或CpG寡脱氧核苷酸1826（TLR9）相结合，并研究它们的物理化学性质及其诱导CD4(+) T细胞的能力。
材料与方法
通过动态光散射和差示扫描量热法对制剂进行研究。通过多重细胞因子分析、酶联免疫吸附测定（ELISA）和细胞内细胞因子染色分析它们对结核抗原诱导CD4(+) T细胞的情况。
结果
DDA/MMG/CpG是获得增强的CD4(+) T细胞反应的最佳组合。然而，将CpG与DDA/MMG脂质体共同配制会导致不稳定，因此使用实验设计对制剂进行了系统优化。
结论
与DDA/MMG脂质体相比，纳米颗粒状的DDA/MMG/CpG佐剂可以实现稳定化，并协同增强CD4(+) T细胞反应。
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