Adjuvant Properties of Aluminum and Calcium Compounds

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Abstract
Aluminum compounds, including aluminum phosphate (AIPO4), aluminum hydroxide [Al(OH)3], and alum-precipitated vaccines (historically referred to as protein aluminate), are currently widely used with human vaccines. These adjuvants have often been referred to as “alum” in the literature. Alum, which chemically is potassium aluminum sulfate [KA1(SO4)2.12H2O], has not been used as an adjuvant as such. Rather, it was used to partially purify protein antigens, mainly tetanus toxoid (TT) and diphtheria toxoid (DT) by precipitating them in the presence of anions including phosphate and bicarbonate ions resulting in a mixture of compounds, mainly aluminum phosphate and aluminum hydroxide (Holt, 1950; Aprile and Wardlaw, 1966). The amounts of aluminum phosphate and aluminum hydroxide in the mixture depended on the amount and nature of anions present in the reaction mixture and adjustment of pH of the final product with sodium hydroxide (Relyveld, 1986; Nicklas, 1992). Although alum-precipitated TT and DT had been used for human immunization for many years, their use has declined considerably because of variations in production of alum-precipitated toxoids (van Ramshorst, 1949; Holt, 1950; Aprile and Wardlaw, 1966; Gupta et al., 1993). Referring to all aluminum adjuvants as “alum” is misleading because aluminum hydroxide and aluminum phosphate have different physical characteristics (see Chapter 9) and differ in their adjuvant properties.