EFFECT OF ANIONS ON MODEL ALUMINUM-ADJUVANT-CONTAINING VACCINES

The effect of adding phosphate, sulfate, or nitrate anions to model al uminum-adjuvant-containing vaccines at pH 7.4 was studied. Three diffe rent aluminum phosphate adjuvants were used that had phosphate to alum inum molar ratios of 1.31, 1.18, and 0.58. One aluminum hydroxide adju vant was used. The isoelectric points of the adjuvants were inversely related to the degree of phosphate substitution for hydroxyl. The addi tion of phosphate anion and to a lesser degree sulfate anion caused ad ditional adsorption of positively charged lysozyme by a model vaccine composed of lysozyme adsorbed by aluminum phosphate adjuvant. The addi tion of phosphate anions and to a lesser degree sulfate anions caused desorption of negatively charged ovalbumin from a model vaccine compos ed of ovalbumin adsorbed by aluminum hydroxide adjuvant. Nitrate anion s had no effect on either model vaccine, The effect of phosphate or su lfate anions did not change as the model lysozyme-aluminum phosphate v accine aged, but it decreased with time in the model ovalbumin-aluminu m hydroxide vaccine. The effect of phosphate or sulfate anions in prod ucing desorption was also influenced by the amount of adsorbed protein . More desorption occurred when the ovalbumin concentration was at the plateau region. The adsorption of phosphate anions was found to lower the isoelectric point of both adjuvants. Thus, one mechanism acting t o produce adsorption or desorption may be an increase in the negative surface charge of the aluminum-containing adjuvants. This in turn decr eased the electrostatic interaction with negatively charged proteins a nd increased the electrostatic interaction with positively charged pro teins. (C) 1995 Academic Press, Inc.