Nanotechnology Research Centre, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2012 Sep;15(5):1032-45.
CpG oligodeoxynucleotides (CpG ODNs) have been shown to have potent immunostimulatory adjuvant activity for a wide range of antigens. Due to susceptibility of phosphodiester CpG ODNs (PO CpG) to nuclease degradation, nuclease-resistant phosphorothioate CpG ODNs (PS CpG) were currently utilized in an in vivo model. In this study, according to some recently reported drawbacks with PS CpG, the adjuvant potential of liposomal PO CpG as a substitute for PS CpG was evaluated.
Soluble Leishmania antigens (SLA) as a model antigen and distearoylphosphatidylcoline (DSPC) as a neutral lipid were employed to prepare liposomes. Susceptible BALB/c mice received buffer, SLA, Lip-SLA, Lip-SLA-PS CpG, Lip-SLA-PO CpG, SLA+PS CpG, or SLA+PO CpG subcutaneously 3 times with 3 weeks intervals and then were challenged with Leishmania major's live promastigotes. Blood and spleen samples were analyzed to determine the level and type of antibodies and cytokines. The number of live parasites in the spleen of immunized mice was determined. Moreover, the lesion size progress was assessed weekly by footpad swelling measurement.
The results showed that mice immunized with Lip-SLA-PS CpG or Lip-SLA-PO CpG developed a significantly smaller footpad swelling, higher level of anti SLA IgG antibodies before and after challenge, and lower spleen parasite burden compared with the control groups. However, there was no significant difference between mice received Lip-SLA-PS CpG and those received Lip-SLA-PO CpG.
The results demonstrated that liposomal PO CpG ODN could be used instead of PS CpG ODN to overcome the possible drawbacks.
CpG 寡脱氧核苷酸（CpG ODN）已被证明对广泛的抗原具有强大的免疫刺激佐剂活性。由于磷酸二酯 CpG ODN（PO CpG）易受核酸酶降解，因此目前在体内模型中使用非磷酸二酯键 CpG ODN（PS CpG）。在这项研究中，根据最近报道的 PS CpG 的一些缺点，评估了脂质体 PO CpG 作为 PS CpG 的替代品的佐剂潜力。
以可溶性利什曼原虫抗原（SLA）作为模型抗原，二硬脂酰基磷脂酰胆碱（DSPC）作为中性脂质，制备脂质体。易感性 BALB/c 小鼠接受缓冲液、SLA、Lip-SLA、Lip-SLA-PS CpG、Lip-SLA-PO CpG、SLA+PS CpG 或 SLA+PO CpG 皮下 3 次，间隔 3 周，然后用活利什曼原虫前鞭毛体攻击。分析血液和脾脏样本以确定抗体和细胞因子的水平和类型。测定免疫小鼠脾脏中活寄生虫的数量。此外，通过足垫肿胀测量每周评估病变大小进展。
结果表明，与对照组相比，用 Lip-SLA-PS CpG 或 Lip-SLA-PO CpG 免疫的小鼠的足垫肿胀明显较小，在挑战前后的抗 SLA IgG 抗体水平较高，脾脏寄生虫负荷较低。然而，接受 Lip-SLA-PS CpG 的小鼠与接受 Lip-SLA-PO CpG 的小鼠之间没有显著差异。
结果表明，脂质体 PO CpG ODN 可以替代 PS CpG ODN 以克服可能的缺点。
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