Abstract
Background: Studies revealing the immune stimulatory properties of aluminium-based adjuvants (ABAs) have been impaired by the absence of simple and reliable methods of tracing the adjuvants and their effect on biochemical processes upon endocytosis. Objective: To verify that labelling of ABAs with lumogallion doesn’t affect the physicochemical properties of the adjuvant; tracing cellular interaction with aluminium adjuvants; explore their effect on metabolic activity upon endocytosis. Methods: Physicochemical characterization by Z-potential and size distribution of ABAs labelled with lumogallion. Cellular interactions with ABAs by flow cytometry and confocal microscopy. Metabolic activity explored by measuring transformation of tetrazolium into formazan. Results: No or minor change of zeta potential and average particle size of lumogallion labelled aluminium oxyhydroxide, AlO(OH) and aluminium hydroxyphosphate, Al(OH)x(PO4)y. Both phagocytosing and non-phagocytosing leukocytes became associated with ABAs at concentrations expected after in vivo administration of a vaccine. The ABAs were relatively toxic, affecting both lymphocytes and monocytes, and Al(OH)x(PO4)y was more toxic than AlO(OH). Endocytosed aluminium adjuvant particles were not secreted from the cells and remained intracellular throughout several cell divisions. The presence of ABAs increased the mitochondrial activity of the monocytic cell line THP-1 and peripheral monocytes, as based on the transformation of tetrazolium into formazan. Conclusion: Lumogallion labelled ABAs is a valuable tool tracing interactions between ABAs and cells. Labelled ABAs can be traced intracellularly and ABAs are likely to remain intracellular for a long period of time. Intracellular ABAs increase the mitochondrial activity and the presence of intracellular Al ions is suggested to cause an increased mitochondrial activity.
Highlights
Aluminium salts were introduced as adjuvants in vaccines by Alexander Glenny in 1926 [1] and aluminium salts are today frequently used in both human and veterinary vaccines
Of the two aluminium salts most commonly used as adjuvants, aluminium oxyhydroxide, (Alhydrogel®), shows a linear increase in fluorescence upon incubation with lumogallion, whereas aluminium hydroxyphosphate, (Adju-Phos®) becomes saturated (Fig. 1)
The results indicate an apparent increased normalized MTT activity ratio for both aluminium based adjuvants1874-2262/18 Bentham Open (ABAs) and the aluminium containing zeolite NaY, whereas the used [8]. Dealuminated zeolite Y (USY) ratio was close to the expected ratio of one
Summary
Aluminium salts were introduced as adjuvants in vaccines by Alexander Glenny in 1926 [1] and aluminium salts are today frequently used in both human and veterinary vaccines. 1874-2262/18 2018 Bentham Open (ABAs) are aluminium oxyhydroxide (AlOOH), in this paper referred to as Alhydrogel®, and aluminium hydroxyphosphate, (Al(OH)x(PO4)y), here referred to as Adju-Phos®, and despite the excessive use of these two types of ABA over decades, knowledge and understanding regarding the mechanisms underlying the immune response induced are surprisingly limited [2]. Pre-labelling of ABA particles with lumogallion creates traceable ABA preparations with, as shown in this paper, physicochemical characteristics almost identical to nonmodified ABAs. Studies revealing the immune stimulatory properties of aluminium-based adjuvants (ABAs) have been impaired by the absence of simple and reliable methods of tracing the adjuvants and their effect on biochemical processes upon endocytosis
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