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Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations

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Abstract

Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al3+ in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

Citation

(2016). Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations. Scientific reports, https://doi.org/10.1038/srep31578

Acceptance Date Jul 26, 2016
Publication Date Aug 12, 2016
Journal Scientific Reports
Print ISSN 2045-2322
Publisher Nature Publishing Group
DOI https://doi.org/10.1038/srep31578
Keywords bioinorganic chemistry; biophysical chemistry; cell-particle interactions; cellular imaging; fluorescence imaging
Publisher URL http://www.nature.com/articles/srep31578#abstract

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