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+Mg2+. We thus confirm that Al(OH)3 activates the complement system and show that the alternative pathway is of major importance.

Peptides, Antibodies, Peptide Antibodies and More

“…Basically, PAbs are produced by injecting an immunogen into an animal along with an adjuvant [87]. Adjuvants are used in the immunization to enhance the immune response [88,89]. Several studies have been conducted to identify the most efficient adjuvant.…”

Genotoxic Effects of Aluminum Chloride and Their Relationship with N-Nitroso-N-Methylurea (NMU)-Induced Breast Cancer in Sprague Dawley Rats

“…Aside from the multiple industrial applications of aluminum, it has applications in different fields including a few uses related to human consumption such as a flocculant in drinking water purification processes, as an adjuvant in vaccine preparation, and as an additive in beverages, foods (e.g., sweets and cheeses), antiperspirants and deodorants, among others [1][2][3][4][5][6][7]. However, the soluble forms of aluminum are considered potentially toxic because of their high water solubility and genotoxic capacity and because of our exposure to these soluble forms at subacute and chronic levels on a daily basis [6,8,9].…”

Polyclonal Peptide Antisera

“…It is a safe adjuvant, also approved for human use, and has few side effects. Al(OH) 3 is known to activate the alternative complement pathway as a major mechanism of action [ 8 ]. Other adjuvants, e.g., Freunds complete/ incomplete adjuvant may be used for special purposes but are not recommended.…”