A comparative study of cationic liposome and niosome-based adjuvant systems for protein subunit vaccines: characterisation, environmental scanning electron microscopy and immunisation studies in mice
A comparative study of cationic liposome and niosome-based adjuvant systems for protein subunit vaccines: characterisation, environmental scanning electron microscopy and immunisation studies in mice
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DOI：
10.1211/jpp.58.6.0009
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发表时间：
2006-06-01
影响因子：
3.3
通讯作者：
Perrie, Yvonne
中科院分区：
文献类型：
--
作者：
Vangala, Anil;Kirby, Daniel;Perrie, Yvonne
由二甲基双十八烷基铵（DDA）组成的囊泡佐剂系统可以促进小鼠对结核疫苗融合蛋白的细胞介导和体液免疫应答。然而，发现这些DDA制剂物理不稳定，在环境储存条件下形成聚集体。因此，需要在不破坏其有效的佐剂性的情况下提高此类系统的稳定性。为此，研究了除胆固醇（Chol）和海藻糖6，6 '-二山嵛酸酯（TDB）之外，还掺入非离子表面活性剂如1-棕榈酰甘油（IMP）对这些疫苗递送系统的稳定性和功效的影响。差示扫描量热法显示，当将IMP和胆固醇（1：1摩尔比）掺入DDA系统中时，基于DDA的囊泡的相变温度（T-c）降低了约12 ℃。透射电子显微镜（TEM）显示，除了MP的DDA囊泡导致在多层囊泡的形成。MP-Chol-DDA-TDB（16：16：4：0.5 μ mol）的环境扫描电子显微镜（ESEM）表明，抗原的掺入导致囊泡的稳定性增加，这可能是由于抗原嵌入囊泡双层内。在4 ℃下，DDA脂质体在28天后显示出显著的囊泡聚集，尽管MP-Chol或TDB的添加显示出抑制这种不稳定性。或者，在25摄氏度下，只有基于MP的系统保持其原始尺寸。囊泡制剂中MP的存在也显示促进抗原的体外持续释放。在小鼠中测试各种系统针对三种亚单位抗原（包括分枝杆菌融合蛋白Ag 85 B-ESAT-6）和两种疟疾抗原（裂殖子表面蛋白1，M5 P1和富含谷氨酸的蛋白，GLURP）的佐剂活性。基于MP和DDA的系统以相当的水平诱导抗体应答，而基于DDA的系统诱导更强大的细胞介导的免疫应答。
Vesicular adjuvant systems composing dimethyldioctadecylammonium (DDA) can promote both cell-mediated and humoral immune responses to the tuberculosis vaccine fusion protein in mice. However, these DDA preparations were found to be physically unstable, forming aggregates under ambient storage conditions. Therefore there is a need to improve the stability of such systems without undermining their potent adjuvanticity. To this end, the effect of incorporating non-ionic surfactants, such as 1-monopalmitoyl glycerol (IMP), in addition to cholesterol (Chol) and trehalose 6,6'-dibehenate (TDB), on the stability and efficacy of these vaccine delivery systems was investigated. Differential scanning calorimetry revealed a reduction in the phase transition temperature (T-c) of DDA-based vesicles by similar to 12 degrees C when IMP and cholesterol (1:1 molar ratio) were incorporated into the DDA system. Transmission electron microscopy (TEM) revealed the addition of MP to DDA vesicles resulted in the formation of multi-lamellar vesicles. Environmental scanning electron microscopy (ESEM) of MP-Chol-DDA-TDB (16:16:4:0.5 mu mol) indicated that incorporation of antigen led to increased stability of the vesicles, perhaps as a result of the antigen embedding within the vesicle bilayers. At 4 degrees C DDA liposomes showed significant vesicle aggregation after 28 days, although addition of MP-Chol or TDB was shown to inhibit this instability. Alternatively, at 25 degrees C only the MP-based systems retained their original size. The presence of MP within the vesicle formulation was also shown to promote a sustained release of antigen in-vitro. The adjuvant activity of various systems was tested in mice against three subunit antigens, including mycobacterial fusion protein Ag85B-ESAT-6, and two malarial antigens (Merozoite surface protein 1, M5P1, and the glutamate rich protein, GLURP). The MP- and DDA-based systems induced antibody responses at comparable levels whereas the DDA-based systems induced more powerful cell-mediated immune responses.