Activation of human monocytes by colloidal aluminium salts

Abstract

Subunit vaccines often contain colloidal aluminium salt-based adjuvants to activate the innate immune system. These aluminium salts consist of micrometre-sized aggregates. It is well known that particle size affects the adjuvant effect of particulate adjuvants. In this study, the activation of human monocytes by hexagonal-shaped gibbsite (ø=210±40 nm) and rod-shaped boehmite (ø= 83±27 nm) was compared with classical aluminium oxyhydroxide adjuvant (alum). To this end, human primary monocytes were cultured in the presence of alum, gibbsite or boehmite. The transcriptome and proteome of the monocytes were investigated by using quantitative polymerase chain reaction and mass spectrometry. Human monocytic THP-1 cells were used to investigate the effect of the particles on cellular maturation, differentiation, activation and cytokine secretion, as measured by flow cytometry and enzyme-linked immuno sorbent assay. Each particle type resulted in a specific gene expression profile. IL-1ß and IL-6 secretion was significantly upregulated by boehmite and alum. Of the seven surface markers investigated, only CD80 was significantly upregulated by alum and none by gibbsite or boehmite. Gibbsite hardly activated the monocytes. Boehmite activated human primary monocytes equally to alum, but induced a much milder stress-related response. Therefore, boehmite was identified as a promising adjuvant candidate.