Characterization of aluminum hydroxide for use as an adjuvant in parenteral vaccines.

Aluminum hydroxide has a long history of use as an adjuvant in parenteral vaccines but the problem of inconsistent antibody production has been frequently noted. Although the mechanism of adjuvant action is not fully understood, it is likely that the surface area, surface charge, and morphology of the aluminum hydroxide are of prime importance. Current understanding of the structure of aluminum hydroxide suggests that controlling the presence of anions which coordinate with aluminum during the precipitation reaction and precipitation at a constant pH will produce an aluminum hydroxide with consistent properties. Techniques are described for determining the surface area of aluminum hydroxide in the unaltered liquid state and the surface charge. The importance of morphology is illustrated by electronmicrographs of two forms of aluminum hydroxide which have the same particle size but different porosity and surface accessibility. The adsorption mechanism of proteins by aluminum hydroxide is discussed using pepsin as a model. Infrared and desorption studies showed that pepsin is adsorbed by anionic ligand exchange with surface aluminum as well as by electrostatic attraction.