Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations.
Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations.
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DOI：
10.1038/srep31578
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发表时间：
2016-08-12
影响因子：
4.6
通讯作者：
Exley C
中科院分区：
文献类型：
--
作者：
Mold M;Shardlow E;Exley C
铝佐剂仍然是疫苗接种和免疫治疗中使用最广泛和最有效的佐剂。本文阐明了氢氧化铝和磷酸氢铝佐剂的粒径分布（PSD），试图将这些特性与接种后观察到的生物反应联系起来。体外实验中，溶酶体环境中Al3+溶解度的提高和可能产生的Al3+与细胞死亡率的增加呈正相关，可能在模拟注射部位产生更大的炎症反应。在体外THP-1细胞模型中，将临床批准的疫苗接种中使用的铝基佐剂（ABAs）的细胞摄取与常用的实验性ABA进行比较。使用lumogallion作为铝的直接荧光分子探针，辅以透射电子显微镜，可以进一步了解由所研究的aba的物理化学变化驱动的内化颗粒的形态。我们证明，并非所有的铝佐剂在注射部位内外的物理性质、生物反应性和潜在毒性方面都是相同的。在THP-1细胞的细胞质中，没有立即产生细胞毒性的高负荷氢氧化铝可能使这种形式的铝佐剂易于随后在全身运输，包括进入大脑。
Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al3+ in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.