Uric acid and the vaccine adjuvant activity of aluminium (oxy)hydroxide nanoparticles

In an effort to improve the adjuvanticity of insoluble aluminium salts, we discovered that the adjuvant activity of aluminium salt nanoparticles is significantly stronger than aluminium salt microparticles, likely related to nanoparticle's stronger ability to directly activate NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome as the nanoparticles are more efficiently taken up by phagocytic cells. Endogenous signals such as uric acid from cell damage or death caused by the cytotoxicity of aluminium salts are thought to indirectly activate inflammasome, prompting us to hypothesise that the potent adjuvant activity of aluminium salt nanoparticles is also related to their ability to stimulate uric acid production. In the present study, we prepared aluminium (oxy)hydroxide nanoparticles (∼ 30-100 nm) and microparticles (X₅₀, 9.43 μm) and showed that intraperitoneal injection of mice with the nanoparticles, absorbed with ovalbumin, led to a significant increase in uric acid level in the peritoneal lavage, whereas the microparticles did not. The aluminium (oxy)hydroxide nanoparticles' ability to stimulate uric acid production was also confirmed in cell culture. We concluded that the stronger adjuvant activity of insoluble aluminium (oxy)hydroxide nanoparticles, relative to microparticles, may be attributed at least in part to their stronger ability to induce endogenous danger signals such as uric acid.