Local tissue irritating effects and adjuvant activities of calcium phosphate and aluminium hydroxide with different physical properties

Abstract

Effects of calcium phosphate and aluminium hydroxide adjuvants with different physical properties were examined in guinea pigs for local histopathological reactions, electron-microscopical changes of macrophages and adjuvanticity on total IgG antibody response to subcutaneously administered ovalbumin (OVA) and tetanus toxoid (TT). Calcium phosphate gel (Ca-gel) induced active inflammatory reactions consisting of neutrophils (pseudoeosinophils) and foamy macrophages associated with many multinuclear giant cells for at least 4 weeks. Aluminium hydroxide gel (Al-gel) also elicited granulomatous inflammatory reactions consisting mainly of macrophages with foamy cytoplasm, small lymphocytes and giant cells at the injection sites for up to 8 weeks or longer. Severity of local tissue irritation due to calcium phosphate gel (Ca-gel) was similar to that due to Al-gel except for the duration of the inflammatory reactions. Calcium phosphate suspension (Ca-sus)-induced local reactions completely ceased by the 4th week, while aluminium hydroxide suspension (Al-sus)-induced reactions were seen up to the 8th week. Electron-microscopical observations showed that both Al-gel and Al-sus caused damage of macrophages. The adjuvant activity of Al-gel for OVA or TT was significantly stronger than that of any other adjuvant material, whereas those of Ca-gel and Ca-sus were not seen at a dose of 3 mg calcium phosphate per millitre. Al-sus-TT at a dose of 3 mg aluminium hydroxide per millilitre induced very low levels of antibody. These results suggest that calcium phosphate adjuvant may not be an useful alternative to Al adjuvant.