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

The optimum formulation of vaccines containing multivalent antigens may require that more than a single type of aluminum-containing adjuvant be used. In some cases, in order to maximize the binding of the negatively charged antigen(s), a positively charged adjuvant such as aluminum hydroxide could be used. In other cases, if the antigen(s) were positively charged, a negatively charged adjuvant such as aluminum phosphate might be preferred. The multivalent vaccine would therefore be prepared by combining the individual monovalent bulks resulting in a suspension consisting of mixed aluminum-containing adjuvants. Studies of such mixed suspensions revealed that some phosphate ions from the aluminum phosphate adjuvant desorbed upon the dilution which occurred when the monovalent bulks were combined. The desorption of phosphate reduced 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 charge. Desorption of the adsorbed antigens may also occur when the monovalent suspensions are mixed. In the model system studied, a significant fraction (25%) of adsorbed lysozyme desorbed from the aluminum phosphate adjuvant upon dilution (1:2). In contrast, almost no bovine serum albumin was desorbed from an aluminum hydroxide adjuvant upon similar dilution. A method based on measuring the electrophoretic mobility of the adjuvants was developed to assess the interactions that take place between the different adjuvants. Rapid aggregation was observed for the system consisting of oppositely charged adjuvants. The rate of aggregation of the positively charged aluminum hydroxide adjuvant with the negatively charged aluminum phosphate adjuvant was reduced by the adsorption of proteins. Colloidal stability was enhanced by increased surface coverage of the proteins on the adjuvants. It was concluded that protein adsorption reduces the rate of aggregation of the mixed adjuvant system by minimizing the difference in surface charge between the aluminum-containing adjuvants and by providing steric repulsion. (C) 1995 Academic Press, Inc.