Toward understanding the mechanism underlying the strong adjuvant activity of aluminum salt nanoparticles.
Toward understanding the mechanism underlying the strong adjuvant activity of aluminum salt nanoparticles.
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DOI：
10.1016/j.vaccine.2016.04.081
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发表时间：
2016-06-08
期刊：
影响因子：
5.5
通讯作者：
Cui Z
中科院分区：
文献类型：
--
作者：
Ruwona TB;Xu H;Li X;Taylor AN;Shi YC;Cui Z
铝盐如羟基氧化铝和羟基磷酸铝是常用的人疫苗佐剂。为了提高铝盐的佐剂活性，我们先前表明羟基氧化铝纳米颗粒的佐剂活性比羟基氧化铝微粒的佐剂活性显著更有效。本研究旨在i）理解羟基氧化铝纳米颗粒相对于微粒的有效佐剂活性的机制，和ii）测试羟基磷酸铝纳米颗粒是否也具有比羟基磷酸铝微粒更有效的佐剂活性。在野生型和NLRP 3缺陷的人THP-1骨髓细胞中，羟基氧化铝纳米颗粒和微粒都通过激活NLRP 3炎性体刺激促炎细胞因子IL-1β的分泌，尽管羟基氧化铝纳米颗粒比微粒更有效，这可能与THP-1细胞对纳米颗粒的摄取高于微粒有关。羟基磷酸铝纳米颗粒在帮助模型抗原溶菌酶刺激特异性抗体应答方面也具有比微粒更有效的佐剂活性，这也可能与其更强的激活NLRP 3炎性体的能力有关。
Aluminum salts such as aluminum oxyhydroxide and aluminum hydroxyphosphate are commonly used human vaccine adjuvants. In an effort to improve the adjuvant activity of aluminum salts, we previously showed that the adjuvant activity of aluminum oxyhydroxide nanoparticles is significantly more potent than that of aluminum oxyhydroxide microparticles. The present study was designed to i) understand the mechanism underlying the potent adjuvant activity of aluminum oxyhydroxide nanoparticles, relative to microparticles, and ii) to test whether aluminum hydroxyphosphate nanoparticles have a more potent adjuvant activity than aluminum hydroxyphosphate microparticles as well. In human THP-1 myeloid cells, wild-type and NLRP3-deficient, both aluminum oxyhydroxide nanoparticles and microparticles stimulate the secretion of proinflammatory cytokine IL-1β by activating NLRP3 inflammasome, although aluminum oxyhydroxide nanoparticles are more potent than microparticles, likely related to the higher uptake of the nanoparticles by the THP-1 cells than the microparticles. Aluminum hydroxyphosphate nanoparticles also have a more potent adjuvant activity than microparticles in helping a model antigen lysozyme to stimulate specific antibody response, again likely related to their stronger ability to activate the NLRP3 inflammasome.