Ruwona Tinashe B, Xu Haiyue, Li Xu, Taylor Amber N, Shi Yan-Chun, Cui Zhengrong
The University of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, TX, United States.
Inner Mongolia Key Laboratory of Molecular Biology, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
Vaccine. 2016 Jun 8;34(27):3059-3067. doi: 10.1016/j.vaccine.2016.04.081. Epub 2016 May 5.
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.
氢氧化铝和磷酸铝等铝盐是常用的人用疫苗佐剂。为了提高铝盐的佐剂活性，我们之前表明，氢氧化铝纳米颗粒的佐剂活性明显强于氢氧化铝微粒。本研究旨在：（i）了解相对于微粒，氢氧化铝纳米颗粒具有强大佐剂活性的潜在机制；（ii）测试磷酸铝纳米颗粒是否也比磷酸铝微粒具有更强的佐剂活性。在野生型和NLRP3缺陷型人THP-1髓样细胞中，氢氧化铝纳米颗粒和微粒均通过激活NLRP3炎性小体刺激促炎细胞因子IL-1β的分泌，尽管氢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。在帮助模型抗原溶菌酶刺激特异性抗体反应方面，磷酸铝纳米颗粒也比微粒具有更强的佐剂活性，这同样可能与其激活NLRP3炎性小体的能力更强有关。
