Aluminum hydroxide adjuvant differentially activates the three complement pathways with major involvement of the alternative pathway

• Published in: PloS one Vol. 8; no. 9; p. e74445
• Main Authors: Güven, Esin, Duus, Karen, Laursen, Inga, Højrup, Peter, Houen, Gunnar
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.09.2013; Public Library of Science (PLoS)
• Subjects: Alternative pathway; Aluminum; Aluminum hydroxide; Aluminum Hydroxide - chemistry; Anaphylatoxins; Antigen presentation; B cells; Biochemistry; Biomedical materials; Chelation; Complement; Complement Activation; Complement C3 - chemistry; Complement C3 - metabolism; Complement C3a - biosynthesis; Complement C3a - chemistry; Complement C5a - biosynthesis; Complement C5a - chemistry; Complement component C3; Complement component C3a; Complement component C5a; Complement Membrane Attack Complex - biosynthesis; Complement Membrane Attack Complex - chemistry; Cytokines; Dendritic cells; Ethylenediaminetetraacetic acids; Humans; Immunology; Lectins; Magnesium; Membrane attack complex; Mode of action; Pathways; Phosphatase; Precipitates; Serum - chemistry; Serum - immunology; Serum - metabolism; Signal transduction; Tetanus; Vaccines; Denmark
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0074445

Al(OH)3 is the most common adjuvant in human vaccines, but its mode of action remains poorly understood. Complement involvement in the adjuvant properties of Al(OH)3 has been suggested in several reports together with a depot effect. It is here confirmed that Al(OH)3 treatment of serum depletes complement components and activates the complement system. We show that complement activation by Al(OH)3 involves the three major pathways by monitoring complement components in Al(OH)3-treated serum and in Al(OH)3-containing precipitates. Al(OH)3 activation of complement results in deposition of C3 cleavage products and membrane attack complex (MAC) and in generation of the anaphylatoxins C3a and C5a. Complement activation was time dependent and inhibited by chelation with EDTA but not EGTA+Mg(2+). We thus confirm that Al(OH)3 activates the complement system and show that the alternative pathway is of major importance.