Aramaki Y, Suda H, Tsuchiya S
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Vaccine. 1995 Dec;13(18):1809-14. doi: 10.1016/0264-410x(95)00117-j.
Adjuvant effect of liposomes was compared to that of aluminium hydroxide (Alum) using ovalbumin (OVA) as a model antigen, and the difference in adjuvanticity of liposomes from Alum has been evaluated on the basis of cytokine production. Both adjuvants enhanced the IgG levels, but a remarkable difference was observed in the production of IgG subclass; Alum enhanced IgG1 levels, and liposomes enhanced IgG2a, IG2b, and IG3 levels. Further, Alum enhanced antigen-specific IgE levels, whereas liposomes did not. To clarify the difference in adjuvant effect of these adjuvants, secretion of cytokines, especially interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) which regulate IgE production, was estimated ex vivo. Overnight culture of splenic cells obtained from mice immunized with liposomes encapsulating OVA elicits IFN-gamma secretion, but not IL-4 secretion. On the other hand, the production of both cytokines was elevated by the immunization with OVA-Alum complex. The results indicate that the difference of adjuvant activity between liposomes and Alum may come from the difference in the secretion of IL-4 and that, consequently, a different class of antibody response is developed. More importantly, negatively charged liposomes containing phosphatidylserine remarkably promoted IFN-gamma secretion compared to neutral liposomes.
以卵清蛋白（OVA）作为模型抗原，比较了脂质体与氢氧化铝（明矾）的佐剂效应，并基于细胞因子产生情况评估了脂质体与明矾佐剂性的差异。两种佐剂均提高了IgG水平，但在IgG亚类产生方面观察到显著差异；明矾提高了IgG1水平，而脂质体提高了IgG2a、IgG2b和IgG3水平。此外，明矾提高了抗原特异性IgE水平，而脂质体则没有。为了阐明这些佐剂在佐剂效应上的差异，对细胞因子的分泌情况进行了体外评估，尤其是对调节IgE产生的干扰素-γ（IFN-γ）和白细胞介素-4（IL-4）。用包裹OVA的脂质体免疫小鼠获得的脾细胞过夜培养可引发IFN-γ分泌，但不引发IL-4分泌。另一方面，用OVA-明矾复合物免疫可提高两种细胞因子的产生。结果表明，脂质体和明矾之间佐剂活性的差异可能源于IL-4分泌的差异，因此会产生不同类型的抗体反应。更重要的是，与中性脂质体相比，含有磷脂酰丝氨酸的带负电荷脂质体显著促进了IFN-γ分泌。
