Aluminum (Oxy)Hydroxide Nanosticks Synthesized in Bicontinuous Reverse Microemulsion Have Potent Vaccine Adjuvant Activity

Insoluble aluminum salts such as aluminum (oxy)hydroxide are commonly used as vaccine adjuvants. Recently, there is evidence suggesting that the adjuvant activity of aluminum salt-based materials is tightly related to their physicochemical properties, including nanometer-scale size, shape with long aspect ratio, and low degree of crystallinity. Herein, for the first time, the bicontinuous reverse microemulsion (RM) technique was utilized to synthesize stick-like monodisperse aluminum (oxy)hydroxide nanoparticles with a long aspect ratio of ∼10, length of ∼80 nm, and low degree of crystallinity (denoted as Al-nanosticks). Moreover, the relationship between the physicochemical properties of Al-nanosticks and the bicontinuous RM was discussed. Compared to the commercial Alhydrogel, which contains micrometer-scale aluminum oxyhydroxide particular aggregates with moderate degree of crystallinity, the Al-nanosticks are more effective in adsorbing and delivering antigens (e.g., ovalbumin, OVA) into antigen-presenting cells, activating inflammasomes, and potentiating OVA-specific antibody responses in a mouse model. It is concluded that the aluminum (oxy)hydroxide nanosticks synthesized in the bicontinuous RM are promising new aluminum salt-based vaccine adjuvants.