Aluminum Hydroxide And Aluminum Phosphate Adjuvants Elicit A Different Innate Immune Response

• Published in: Journal of pharmaceutical sciences Vol. 111; no. 4; pp. 982 - 990
• Main Authors: Kooijman, Sietske, Vrieling, Hilde, Verhagen, Lisa, de Ridder, Justin, de Haan, Alex, van Riet, Elly, Heck, Albert J.R., Kersten, Gideon F.A., Pennings, Jeroen L.A., Metz, Bernard, Meiring, Hugo D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2022
• Subjects: Adjuvants, Immunologic - pharmacology; Adjuvants, Pharmaceutic; Aluminum; Aluminum Compounds; Aluminum hydroxide; Aluminum Hydroxide - pharmacology; Aluminum phosphate; Humans; Immunity, Innate; Innate immune response(s); Liquid chromatography-mass spectrometry (LC-MS); Phosphates; Proteome; Vaccine adjuvants; Liquid chromatography-mass spectrometry (LC-MS); Innate immune response(s); Vaccine adjuvants; Aluminum phosphate; Aluminum hydroxide
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2022.01.014

Aluminum hydroxide (Al(OH)3) and aluminum phosphate (AlPO4) are widely used adjuvants in human vaccines. However, a rationale to choose one or the other is lacking since the differences between molecular mechanisms of action of these adjuvants are unknown. In the current study, we compared the innate immune response induced by both adjuvants in vitro and in vivo. Proteome analysis of human primary monocytes was used to determine the immunological pathways activated by these adjuvants. Subsequently, analysis of immune cells present at the site of injection and proteome analysis of the muscle tissue revealed the differentially regulated processes related to the innate immune response in vivo. Incubation with Al(OH)3 specifically enhanced the activation of antigen processing and presentation pathways in vitro. In vivo experiments showed that only intramuscular (I.M.) immunization with Al(OH)3 attracted neutrophils, while I.M. immunization with AlPO4 attracted monocytes/macrophages to the site of injection. In addition, only I.M. immunization with Al(OH)3 enhanced the process of hemostasis after 96 hours, possibly related to neutrophilic extracellular trap formation. Both adjuvants differentially regulated various immune system-related processes. The results show that Al(OH)3 and AlPO4 act differently on the innate immune system. We speculate that these different regulations affect the interaction with cells, due to the different physicochemical properties of both adjuvants.