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Author
Title Investigating the use of gold nanoparticles in vaccine delivery
URL
Publication Date
Degree PhD
Degree Level doctoral
University/Publisher University of Exeter
Abstract Vaccination is one of the most effective public health interventions in the world, saving millions of lives and preventing the onset of debilitating diseases. With widespread emergence of multi-drug resistant pathogens, the importance of preventative medicine has become even more apparent. However, one of the limiting factors in developing novel vaccines that are both safe and highly immunogenic is the availability of adjuvant delivery systems licensed for human use. The purpose of this study was to investigate the role gold nanoparticles could play as an effective vaccine delivery system. A variety of coupling chemistries were explored for their ability to conjugate protein and polysaccharide antigens onto the surface of gold nanoparticles for the development of vaccines against a number of biologically important human pathogens including Y. pestis, B. mallei and S. pneumoniae. Retention of antigenicity and coupling efficiency of conjugated molecules was measured using characterisation techniques such as localised surface plasmon resonance and immunoblotting. Gold nanoparticle coupled antigens were then used to immunise mice and to measure the protective efficacy and the immunological response induced. The findings indicate antigen-specific immune responses are elevated when an antigen is coupled onto gold nanoparticles. Moreover, immunological data from nanoparticle coupled glycoconjugate vaccines against B. mallei and S. pneumoniae indicate the likely presence of a strong T cell immune response which is essential for providing immunological memory. Finally, an intracellular trafficking assay was carried out to identify some of the mechanisms that might be involved in uptake of gold nanoparticles into professional phagocytes. Confocal imaging of receptors associated with endosomal compartments revealed that gold nanoparticles may enter cells through multiple pathways. The findings reported in this study suggest that gold nanoparticles may be an excellent candidate for further investigation as a novel vaccine delivery system.
Subjects/Keywords 620.5; Gold nanoparticles ; Vaccine ; Glycoconjugate ; Plague ; Glanders ; Pneumococcus
Rights Full text available
Country of Publication uk
Record ID handle:10871/14528
Repository ethos
Date Retrieved
Date Indexed 2016-10-03

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…5.1 Introduction 122 5.1.1 Pneumococcus 122 5.1.2 Pneumococcal vaccines 125 5.1.3 Objectives 126 Materials and methods 127 CPS coupling onto gold nanoparticles 127 Results 129 5.3.1 CPS conjugation 129 5.3.2 Glycoconjugate

…59 Figure 3.16 MALDI-TOF spectra for AuNP-F1 61 Figure 3.17 F1 specific IgG concentration 63 Figure 3.18 Competitive ELISA for binding to F1 65 Figure 3.19 F1 specific IgG concentration over time 73 Chapter 4 A Glycoconjugate Vaccine…

…subclass concentration, study 2 111 Figure 4.19 LPS-IgG isotypes 112 Figure 4.20 IgM concentration, study Chapter 5 A Glycoconjugate Vaccine against Pneumococcus122 Figure 5.1 Disease associated serotypes of pneumococcus 123 Figure 5.2 Plasmon…

…reductive amination coupling 135 viii 1 1 2 2 2 99 110 113 Figure 5.7 Western blot for CPS glycoconjugate 136 Figure 5.8 IgG concentration 138 Figure 5.9 CPS specific IgG concentration 139 Figure 5.10 IgM concentration 140 Figure 5.11…

…4 A Glycoconjugate Vaccine against Glanders 75 Table 4.1 Summary of results from “immunisation study 1” 106 Table 4.2 Summary of results from “immunisation study 2” 114 Chapter 5 A Glycoconjugate Vaccine against Pneumococcus 122 Table 5.1…

…x5D;. However, by conjugating polysaccharides to a protein carrier (glycoconjugate) peptide antigens are recognised by CD4+ or CD8+ T cells and elicit a B cell response in a Tdependent manner [64]. For vaccines against intracellular…

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