Adsorption and Desorption of Immune-Modulating Substances by Aluminium-Based Adjuvants: An Overlooked Feature of the Immune-Stimulating Mechanisms of Aluminium-Based Adjuvants

Vaccine antigens are partly adsorbed onto aluminium-based adjuvant particles, forming an unstable corona. At the inoculation site, the corona will be restructured, and the adsorbed antigens will be released through replacement with biomolecules from the interstitial fluid of the recipient. Aluminium-based adjuvants (ABAs) carrying a corona of serum proteins as a model of particles with a pre-formed antigen corona were shown to adsorb several categories of cytokines and growth factors, as assessed from a protein array covering 18 different analytes. Out of the 18 analytes, 12 were shown to be adsorbed by the aluminium-based adjuvant Alhydrogel (R), which had a pre-formed protein corona. The adsorption of TNF-alpha, IL-2, IL-4, IL-10, and IFN-gamma was studied in detail. Among the studied cytokines, IL-2, IL-4, and IFN-gamma, were adsorbed by Alhydrogel (R). Adsorbed IFN-gamma was further studied to show that the adsorption of IFN-gamma did not denature the cytokine, and the cytokine could be desorbed from adjuvant particles in a biologically active form and in relevant amounts. The adsorption of immune-stimulating molecules onto ABAs at the administration site of a vaccine is a neglected event in the mode of action of aluminium-based adjuvants. This process may modulate the immune response with a profound impact on initiating the innate immune response and consequently the adaptive immune response.