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

Esin Güven, Karen Duus, Inga Laursen, Peter Højrup, Gunnar Houen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.
Original languageEnglish
JournalPLOS ONE
Volume8
Issue number9
Pages (from-to)e74445
ISSN1932-6203
DOIs
Publication statusPublished - 2013

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Aluminum Hydroxide
aluminum hydroxide
adjuvants
complement
Chemical activation
Anaphylatoxins
Complement Membrane Attack Complex
Complement C3
Egtazic Acid
Chelation
Serum
Edetic Acid
Precipitates
Vaccines
Monitoring
chelation
mechanism of action
indium(III) hydroxide
vaccines
monitoring

Cite this

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title = "Aluminum hydroxide adjuvant differentially activates the three complement pathways with major involvement of the alternative pathway",
abstract = "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.",
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Aluminum hydroxide adjuvant differentially activates the three complement pathways with major involvement of the alternative pathway. / Güven, Esin; Duus, Karen; Laursen, Inga; Højrup, Peter; Houen, Gunnar.

In: PLOS ONE, Vol. 8, No. 9, 2013, p. e74445.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Aluminum hydroxide adjuvant differentially activates the three complement pathways with major involvement of the alternative pathway

AU - Güven, Esin

AU - Duus, Karen

AU - Laursen, Inga

AU - Højrup, Peter

AU - Houen, Gunnar

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

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