Toward understanding the mechanism underlying the strong adjuvant activity of aluminum salt nanoparticles

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• 作者：Tinashe B. Ruwona^a ; Haiyue Xu^a ; Xu Li^a ; Amber N. Taylor^a ; Yan-chun Shi^b ; ^{Ycshi5388@163.com" class="auth_mail" title="E-mail the corresponding author} ; Zhengrong Cui^a ; ^b ; ^{Zhengrong.cui@austin.utexas.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Aluminum oxyhydroxide ; Aluminum hydroxyphosphate ; Nanoparticles ; Microparticles ; IL-1β ; NLRP3 inflammasome ; Antigen binding ; Antibody response
• 刊名：Vaccine
• 出版年：2016
• 出版时间：8 June 2016
• 年：2016
• 卷：34
• 期：27
• 页码：3059-3067
• 全文大小：1913 K

文摘

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.