Maughan, CN; (2017) Experimental and in silico computational studies of novel nanoparticle vaccine adjuvants. Doctoral thesis , UCL (University College London).

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Abstract

This thesis applies inorganic chemistry to develop new nanoparticulate vaccine adjuvants, entities added to a vaccine to inculcate robust immunity. The Introduction sets out the background to this work, and the Experimental Methods chapter reviews the techniques applied. Chapter 3 then reports the preparation of AlO(OH) using a continuous hydrothermal synthetic pathway – with sub-100 °C temperatures and atmospheric pressure – to produce nanoscale particles. A variety of experimental parameters was explored, and some degree of particle engineering could be achieved albeit over a narrow range of sizes and shapes. There was some evidence of particle size influencing the response of macrophages to the samples. Chapter 4 and Chapter 5 aim to engineer the size and shape of hydroxyapatite and zinc oxide nanoparticles, respectively, through different continuous hydrothermal processes. Several different morphologies (spheres, and mixtures of spheres/rods/platelets) could be produced. The morphology and particle size appear to affect cytokine production in vitro. Chapter 6 explores layered double hydroxides (LDHs) as inorganic adjuvants. A series of materials were prepared and characterised, and the effect of changing the LDH chemical composition on adjuvanticity determined. It was found that the size of the guest anion influences the immune response. Further, computational models were developed to aid the in silico prediction of immunogenicity, with calculated energy values being a suitable proxy for the zeta potential. The related hydroxy double salt (HDS) materials are investigated as adjuvants in Chapter 7. A series of materials was prepared and their chemical composition found to markedly effect the immune response in vitro. Computational models were sought with the same in silico aim as the LDH materials, however with limited success owing to a lack of detailed structural knowledge in the literature. Finally, overarching conclusions and suggestions for the future outlook of this area of research are given in Chapter 8.

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