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Title: Elucidating the bioinorganic chemistry of aluminium-based adjuvants : the influence of physicochemical characteristics upon events following simulated in vitro vaccination
Author: Shardlow, Emma Mary
ISNI:       0000 0004 6422 9998
Awarding Body: Keele University
Current Institution: Keele University
Date of Award: 2016
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Despite their essential role and widespread use within clinical vaccinations, the bioinorganic chemistry of aluminium salts at the injection site remains elusive due to a lack of information concerning their physicochemical properties. Such information is essential in order to understand how these materials interact with the physiological environment and potentiate an immunological response, which is still not fully understood. These properties were extensively studied herein in order to elucidate the relationship between adjuvant physicochemistry and the events occurring post vaccination. While characterisation of zeta potential and surface functionality were both undertaken, experiments focused upon the determination of novel compositional information regarding the PSD of aluminium adjuvants. This approach involved the use of optimised DLS, TEM and filtration-GFAAS. Following characterisation, the cellular uptake and toxicological impact of aluminium salts upon model phagocytic cells (THP-1) was evaluated using lumogallion tracing and a live/dead assay respectively. Alhydrogel and Adju-Phos presented as micron sized, negatively charged aggregates in biological fluid with predominant populations existing < 2.7μm and > 5.6μm respectively following 1hr exposure. Generation of Al3+ was limited within this environment (< 1μg/mL over 72hrs) and both adjuvants were visible within the cytoplasm of phagocytes following 24hrs exposure, although the uptake of particles < 2.7μm was considered preferable. Adju-Phos induced higher toxicity at aluminium concentrations used clinically (100μg/mL) and promoted higher levels of metabolic activity and chemokine production (MCP-1 & MIP-1α), which were attributed to its enhanced intracellular solubility and bioavailability. These studies have shown that surface functionality, solubility and particle size, but not zeta potential play a significant role in the toxicological and immunological response to aluminium salts in vitro. These parameters should be considered in future studies attempting to elucidate the biological mechanisms involved in adjuvant immunopotentiation and those dedicated to the development of safer and more efficient vaccine adjuvants.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD415 Biochemistry