Physico-chemical properties of aluminum adjuvants in vaccines: Implications for toxicological evaluation

Advances on the early cellular events occurring upon exposure of human macrophages to aluminum oxyhydroxide adjuvant

“…In the latter study, AH was internalized 48 h after treatment and remained intracellular at least a week after replacement of the medium. Using a 25-fold higher concentration of AH (ie 50 µg Al/ml), we observed that AH was already captured by PBMCs 29,42 . However, it should be noted that a conversion of the charge, from negatively to positively charged, of AH particles in the culture medium has been reported by Mold et al 43 .…”

“…Moreover, the presence of the antigens in vaccines can modify the size of particles and lead to the formation of aggregates of larger particles, which can also have an effect on certain cellular mechanisms such as aforementioned LAP or autophagy and cellular cytotoxicity 29 . In addition to the presence of antigens, the dilution has a real impact in the size of particles and the greater the dilution is, the more the aggregates will dissociate to form smaller particle sizes 29 . So, the size of particles in the whole vaccine (500 µg Al 3+ /ml) differs than the size of particles in the diluted solutions (50 µg Al 3+ /ml).…”

“…Phagocytosis observation was performed in Ibidi blade, cytokines assay and western blot in 24 wells culture plates, ROS assay in 96 wells culture plates, and mitochondrial metabolism evaluation in Seahorse XFe24 culture plates. After 3 h of adherence, culture medium was gently removed and replaced by a 37 °C differentiation medium composed of RPMI 1640 ATCC Modification with 1% of penicillin/streptomycin, 29,42 .…”

“…This association was based on the immune stimulating properties of the crystallized uric acid acting as a danger associated molecular pattern which is highly pro-inflammatory after cell recognition 27,28 . After phagocytosis, the crystalline structure of ABAs (especially for AH 29 ) could disrupt membranes leading to inflammation and cell death by both apoptosis and pyroptosis 30 , APCs maturation and therefore antibody production. This assumption was further supported by host DNA release at the AH injection site 31 .…”

Proton-Gradient-Driven Porphyrin-Based Liposome Remote-Loaded with Imiquimod as In Situ Nanoadjuvants for Synergistically Augmented Tumor Photoimmunotherapy

“…Adjuvants can effectively improve the efficiency of antigen presentation and thus play a crucial role in tumor immunotherapy. , At present, only aluminum adjuvant has been approved by the FDA for clinical application . Aluminum adjuvant can only activate humoral immunity but cannot activate cellular immunity, and the dosage form of aluminum adjuvant is limited to suspension, emulsion, etc., which limits clinical application. , Toll-like receptor (TLR) agonists can activate a family of transmembrane receptors that are expressed on immune and nonimmune cells, such as TLR2 agonist lysophosphatidic acid, TLR3 agonist [polyinosinic acid-polycytidylic acid (poly-IC)], TLR4 agonist [lipopolysaccharide (LPS)], TLR5 agonist [recombinant flagellin (CBLB502)], TLR7/8 agonist (imiquimod, R837), and TLR9 agonist [family CpG oligodeoxynucleotides (CpG ODN)], − and activated TLRs are able to recognize pathogen-associated molecular pattern molecules and damage-associated molecular pattern molecules.…”