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.

Toward understanding the mechanism underlying the strong adjuvant activity of aluminum salt nanoparticles. Ruwona TB, Xu H, Li X, Taylor AN, Shi Y, Cui Z. Vaccine 2016;34:3059–67

“…Similarly, we also showed that the AH-NPs (majority below 100 nm) are more potent than the AH-MPs (X 50 , 5.36 μm) in activating NLRP3 inflammasome [3]. Based on the findings, we concluded that the mechanism underlying the stronger adjuvant activity of aluminum salt nanoparticles is likely related to their stronger ability to activate the NLRP3 inflammasome than aluminum salt microparticles [3]. …”

“…The paper commented by Mold et al was designed to understand the potential mechanism underlying the stronger vaccine adjuvant activity of AH-NPs, relative to AH-MPs, and to test whether aluminum phosphate nanoparticles also have a stronger adjuvant activity than aluminum phosphate microparticles [3]. We prepared aluminum phosphate nanoparticles (AP-NPs, 122–255 nm) and aluminum phosphate microparticles (AP-MPs, X 50 , 4.87 μm), and showed that the AP-NPs are more potent than the AP-MPs in activating NLRP3 inflammasome [3]. Similarly, we also showed that the AH-NPs (majority below 100 nm) are more potent than the AH-MPs (X 50 , 5.36 μm) in activating NLRP3 inflammasome [3].…”

“…We prepared aluminum phosphate nanoparticles (AP-NPs, 122–255 nm) and aluminum phosphate microparticles (AP-MPs, X 50 , 4.87 μm), and showed that the AP-NPs are more potent than the AP-MPs in activating NLRP3 inflammasome [3]. Similarly, we also showed that the AH-NPs (majority below 100 nm) are more potent than the AH-MPs (X 50 , 5.36 μm) in activating NLRP3 inflammasome [3]. Based on the findings, we concluded that the mechanism underlying the stronger adjuvant activity of aluminum salt nanoparticles is likely related to their stronger ability to activate the NLRP3 inflammasome than aluminum salt microparticles [3].…”

Risk Factors in Induction and Progression of Alzheimer’s Disease: Impacton Protection and Disease-Modifying Factors

“…Aluminum is a constituent of antacids, deodorants and food additives, thus allowed its easy access into the body. Excessive Al intake leads to accumulation of Aβ in the brain and over expression of β-amyloid precursor protein [11]. The neurotoxicity of Aβ is strongly related to oxidative stress which plays an effective role in the pathogenesis of AD [12].…”

Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes

“…20 It has been shown that the NLRP3 inflammasome is activated by classical adjuvants, including aluminum hydroxide and saponin, which requires both Toll-like receptor (TLR) and NLRP3 signaling in APCs. [21][22][23][24] Following the recruitment and activation of caspase-1 in the NLRP3 inflammasome pathway, the biologically inactive precursor pro-IL-1β is processed into IL-1β. In fact, chitosan or SiO 2 nanoparticles are known to trigger caspase-1 cleavage and IL-1β secretion in macrophages and keratinocytes, which are mediated by the NLRP3 inflammasome.…”