title: 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 millilitre. 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.
authors.affiliation: Department of Safety Research on Biologics, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Goto
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: J
authors.initials: J
authors.lastname: Maeyama
authors.forename: M
authors.initials: M
authors.lastname: Shibano
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: J
authors.initials: J
authors.lastname: Yamaguchi
authors.forename: S
authors.initials: S
authors.lastname: Yoshihara
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000536:Aluminum Hydroxide / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D002130:Calcium Phosphates / Q000494:pharmacology / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000097:blood; D007509:Irritants / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D010047:Ovalbumin / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D002130:Calcium Phosphates; D007074:Immunoglobulin G; D007509:Irritants; D013745:Tetanus Toxoid; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D000536:Aluminum Hydroxide; C485838:calcium phosphate, monobasic, anhydrous; D010047:Ovalbumin; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous