title: Toward understanding the mechanism underlying the strong adjuvant activity of aluminum salt nanoparticles.
abstract: 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.
authors.affiliation: The University of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, TX, United States.
authors.forename: Tinashe B
authors.initials: TB
authors.lastname: Ruwona
authors.affiliation: The University of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, TX, United States.
authors.forename: Haiyue
authors.initials: H
authors.lastname: Xu
authors.affiliation: The University of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, TX, United States.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: The University of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, TX, United States.
authors.forename: Amber N
authors.initials: AN
authors.lastname: Taylor
authors.affiliation: Inner Mongolia Key Laboratory of Molecular Biology, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China. Electronic address: Ycshi5388@163.com.
authors.forename: Yan-Chun
authors.initials: YC
authors.lastname: Shi
authors.affiliation: 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. Electronic address: Zhengrong.cui@austin.utexas.edu.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Cui
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation; D002460:Cell Line; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000276:immunology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000276:immunology; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; C508585:IL1B protein, human; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human
keywords: Aluminum hydroxyphosphate; Aluminum oxyhydroxide; Antibody response; Antigen binding; IL-1β; Microparticles; NLRP3 inflammasome; Nanoparticles