Aluminum hydroxide nanoparticles show a stronger vaccine adjuvant activity than traditional aluminum hydroxide microparticles

• Published in: Journal of controlled release 2014-01, Vol.173, p.148-157
• Main Authors: Li, Xinran, Aldayel, Abdulaziz M., Cui, Zhengrong
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - pharmacology; Aluminum Hydroxide - administration & dosage; Aluminum Hydroxide - immunology; Animals; Anthrax - immunology; Anthrax - prevention & control; Anthrax Vaccines - administration & dosage; Anthrax Vaccines - immunology; Antibody Formation; Antibody responses; Antigens, Bacterial - administration & dosage; Antigens, Bacterial - immunology; Bacillus anthracis; Bacillus anthracis - immunology; Bacterial Toxins - administration & dosage; Bacterial Toxins - immunology; Cell Line; Cells, Cultured; Female; Humans; Local inflammation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microparticles; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - metabolism; Nanoparticles - ultrastructure; Ovalbumin - administration & dosage; Ovalbumin - immunology; Particle Size; Vaccine; Vaccines - administration & dosage; Vaccines - immunology
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2013.10.032

Aluminum hydroxide is used as a vaccine adjuvant in various human vaccines. Unfortunately, despite its favorable safety profile, aluminum hydroxide can only weakly or moderately potentiate antigen-specific antibody responses. When dispersed in an aqueous solution, aluminum hydroxide forms particulates of 1–20μm. There is increasing evidence that nanoparticles around or less than 200nm as vaccine or antigen carriers have a more potent adjuvant activity than large microparticles. In the present study, we synthesized aluminum hydroxide nanoparticles of 112nm. Using ovalbumin and Bacillus anthracis protective antigen protein as model antigens, we showed that protein antigens adsorbed on the aluminum hydroxide nanoparticles induced a stronger antigen-specific antibody response than the same protein antigens adsorbed on the traditional aluminum hydroxide microparticles of around 9.3μm. The potent adjuvant activity of the aluminum hydroxide nanoparticles was likely related to their ability to more effectively facilitate the uptake of the antigens adsorbed on them by antigen-presenting cells. Finally, the local inflammation induced by aluminum hydroxide nanoparticles in the injection sites was milder than that induced by microparticles. Simply reducing the particle size of the traditional aluminum hydroxide adjuvant into nanometers represents a novel and effective approach to improve its adjuvanticity. [Display omitted]