INTERACTIONS IN MODEL VACCINES COMPOSED OF MIXTURES OF ALUMINUM-CONTAINING ADJUVANTS

The optimum formulation of vaccines containing multivalent antigens ma y require that more than a single type of aluminum-containing adjuvant be used. In some cases, in order to maximize the binding of the negat ively charged antigen(s), a positively charged adjuvant such as alumin um hydroxide could be used. In other cases, if the antigen(s) were pos itively charged, a negatively charged adjuvant such as aluminum phosph ate might be preferred. The multivalent vaccine would therefore be pre pared by combining the individual monovalent bulks resulting in a susp ension consisting of mixed aluminum-containing adjuvants. Studies of s uch mixed suspensions revealed that some phosphate ions from the alumi num phosphate adjuvant desorbed upon the dilution which occurred when the monovalent bulks were combined. The desorption of phosphate reduce d the negative surface charge of the aluminum phosphate adjuvant. The desorbed phosphate anions were subsequently readsorbed by the aluminum hydroxide adjuvant resulting in a decrease of its positive surface ch arge. Desorption of the adsorbed antigens may also occur when the mono valent suspensions are mixed. In the model system studied, a significa nt fraction (25%) of adsorbed lysozyme desorbed from the aluminum phos phate adjuvant upon dilution (1:2). In contrast, almost no bovine seru m albumin was desorbed from an aluminum hydroxide adjuvant upon simila r dilution. A method based on measuring the electrophoretic mobility o f the adjuvants was developed to assess the interactions that take pla ce between the different adjuvants. Rapid aggregation was observed for the system consisting of oppositely charged adjuvants. The rate of ag gregation of the positively charged aluminum hydroxide adjuvant with t he negatively charged aluminum phosphate adjuvant was reduced by the a dsorption of proteins. Colloidal stability was enhanced by increased s urface coverage of the proteins on the adjuvants. It was concluded tha t protein adsorption reduces the rate of aggregation of the mixed adju vant system by minimizing the difference in surface charge between the aluminum-containing adjuvants and by providing steric repulsion. (C) 1995 Academic Press, Inc.