City Research Online

Abstract

This study has used in vitro models to test the immunogenicity of novel vaccines against TB and Dengue Fever. Initially murine dendritic cells were used to model the immunogenicity of novel vaccines candidates and an array of potential adjuvants. Three vaccine candidates, Spore FP1, YC NaMa FP1 and Liposome FP1 were found to be immunogenic, increasing expression of DC activation markers and production of proinflammatory cytokines.

Further vaccine testing was carried out using in vitro models based on human tonsillar mononuclear cells (TMCs). These cells were first characterised and then used to establish immunogenicity models for TB and dengue fever. In this model, the BCG vaccine elicited IFNy, IL-17 responses and proliferative responses. The novel vaccine candidates Spore FP1, YC NaMa FP1, Liposome FP1, IgA ICM were all immunogenic, generating IFNy responses. The Dengue vaccine candidate DERICS elicited IFNy and IL-4 responses in CD4+ T cells. Another candidate, D-PIGS, generated IL-4, IFNy and TNFa responses.

This study developed a mycobacterial infection model using TMCs. This model examined the activation of monocytes and their ability to eliminate mycobacteria. Novel TB vaccines were applied to this model. The BCG vaccine activated monocytes and promoted the clearance of intracellular mycobacteria. Similarly, the novel vaccine candidates Spore FP1, YC NaMa FP1 and Liposome FP1 were also able to activate monocytes and enhance their ability to clear mycobacterial infection.

In the course of this study, it was discovered that GFP BCG directly interact with human B cells. Further investigation revealed that BCG binds to the cell surface but is not internalised by B cells. This interaction is mediated by antibodies and has a profound suppressive effect on B cells. This finding may have implications for our understanding of the humoral response following BCG vaccination. These studies demonstrate that human TMC in vitro models can play a useful role in early vaccine development.

Publication Type:	Thesis (Doctoral)
Subjects:	Q Science > QR Microbiology Q Science > QR Microbiology > QR180 Immunology Q Science > QR Microbiology > QR355 Virology
Departments:	School of Health & Medical Sciences > Infection and Immunity Research Institute School of Health & Medical Sciences > School of Health & Medical Sciences Doctoral Theses Doctoral Theses

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