Aluminum Compounds as Vaccine Adjuvants

Aluminum compounds, including aluminum phosphate (AlPO₄ ), aluminum hydroxide (Al(OH)₃ ), and alum precipitated vaccines, historically referred to as protein aluminate, are currently the most commonly used adjuvants with human and veterinary vaccines (1 –6 ). These adjuvants are often referred to as “alum” in the literature, which is misleading because (1) two most widely used adjuvants from this group, aluminum hydroxide and aluminum phosphate, have very different physical characteristics (7 ) and differ in their adjuvant properties (3 ,6 ); and (2) alum, chemically potassium aluminum sulfate (KAl(SO₄ )₂ .12H₂ O), has not been used as an adjuvant as such. Alum was originally used to partially purify protein antigens, mainly tetanus and diphtheria toxoids, by precipitating them in the presence of anions including phosphate, sulphate, and bicarbonate ions resulting in a mixture of compounds, mainly aluminum phosphate and aluminum hydroxide (4 ,8 ,9 ). The amounts of aluminum phosphate and aluminum hydroxide in the mixture depended upon the amount and nature of anions present in the reaction mixture and adjustment of pH of the final product with sodium hydroxide (3 ,4 ,6 ,10 ,11 ). Although alum-precipitated tetanus and diphtheria toxoids had been used for human immunization for many years, their use has declined considerably because of variability in production of alum precipitated toxoids (1 ,4 ,8 ,9 ,12 ).