Effect of microenvironment pH of aluminum hydroxide adjuvant on the chemical stability of adsorbed antigen.

The rate of acid-catalyzed hydrolysis of glucose-1-phosphate (G1P) when adsorbed to aluminum hydroxide adjuvant was significantly slower than the rate of hydrolysis of a solution of G1P at the same pH. It was concluded that the positively charged aluminum hydroxide adjuvant (iep 11.4) electrostatically attracted anions including hydroxyls to form a double layer surrounding the adjuvant particles. Thus, the pH of the microenvironment surrounding the aluminum hydroxide adjuvant was higher than the bulk pH. Adsorbed G1P hydrolyzed at a rate associated with the pH of the microenvironment of the surface of the adjuvant rather than with the pH of the bulk solution. Comparison of the rate constant for the hydrolysis of adsorbed G1P to the pH-stability profile of G1P in solution revealed that adsorbed G1P hydrolyzed at a rate associated with a pH that was approximately two pH units higher than the bulk pH. The results suggest that the chemical stability of antigens that degrade by pH-dependent mechanisms can be optimized by modifying the surface charge of the aluminum-containing adjuvant to produce the pH of maximum stability in the microenvironment of the adjuvant.