Activation of Human Monocytes by Colloidal Aluminum Salts

• Published in: Journal of pharmaceutical sciences Vol. 109; no. 1; pp. 750 - 760
• Main Authors: Vrieling, Hilde, Kooijman, Sietske, de Ridder, Justin W., Thies-Weesie, Dominique M.E., Soema, Peter C., Jiskoot, Wim, van Riet, Elly, Heck, Albert J.R., Philipse, Albert P., Kersten, Gideon F.A., Meiring, Hugo D., Pennings, Jeroen L., Metz, Bernard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2020
• Subjects: Adjuvants, Immunologic - chemistry; Adjuvants, Immunologic - pharmacology; alum; aluminum hydroxide; Aluminum Hydroxide - chemistry; Aluminum Hydroxide - pharmacology; Aluminum Oxide - chemistry; Aluminum Oxide - pharmacology; B7-1 Antigen - genetics; B7-1 Antigen - metabolism; Cell Differentiation - drug effects; Colloids; Drug Compounding; Humans; immune responses; Immunity, Innate - drug effects; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Monocytes - drug effects; Monocytes - immunology; Monocytes - metabolism; Particle Size; proteomic; THP-1 Cells; Transcriptome; vaccine adjuvants; proteomic; aluminum hydroxide; colloids; alum; vaccine adjuvants; immune responses
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2019.08.014

Subunit vaccines often contain colloidal aluminum salt–based adjuvants to activate the innate immune system. These aluminum salts consist of micrometer-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 ± 827 nm) was compared with classical aluminum 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 immunosorbent 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 7 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.