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

Matthew Mold,Christopher Exley,Emma Shardlow

doi:10.1038/srep31578

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.

Highlights

Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy
Whilst a consensus upon the immunomodulatory mechanism of action of Aluminium based adjuvants (ABA) has yet to be reached, it has become increasingly recognised that activation of the innate immune response is crucial for increased antibody titres[1,2]
The continued and widespread use of ABA has followed the emergence of recombinantly expressed protein antigens of high purity as a safer alternative to inactivated or attenuated pathogens[2,3]

Summary

Introduction

Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. 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. Aluminium based adjuvants (ABA) are included in human vaccinations to boost or potentiate the immune response, to the injected antigen[1]. Combined with the relatively low cost of hydrated colloidal aluminium salts and their ease of inclusion as effective adjuvants within clinically approved vaccine formulations, the continued use of ABA in human vaccinations is likely to continue[1,2,4]. The adsorptive capacity of an ABA to its antigen, dictates its choice in studies of adjuvanticity.

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Results

Conclusion