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Title: Phenotypic and functional characterisation of innate and adaptive immune responses after mucosal vaccination
Author: Hall, L. J.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2007
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Here I examine the properties of a live Salmonella-based vaccine and a mucosal adjuvant based on a bacterial protein. Initially I examined the immunogenicity of the M. tuberculosis fusion antigen Ag85B-ESAT6 using a number of different mucosal vaccination strategies. These strategies included (i) intranasal immunisation with Ag85B-ESAT6 protein with and without Heat Labile toxin as an adjuvant (ii) oral immunisation with Salmonella enterica Typhimurium expressing Ag85B-ESAT6 from in vivo inducible or constitutive promoters (with and without intranasal boosts). Mice immunised with the various vaccine candidates were found to have significant anti-Ag85B-ESAT6 serum and mucosal antibody titres as well as strong TH1 type cytokine responses, with IFN-γ levels particularly high. Intranasal boosting served to further enhance these immune responses. Following vaccination with the constitutive Salmonella vector, mice challenged with M. tuberculosis were found to have significantly reduced CFU in the liver when compared to non-vaccinated animals. Mice primed with Salmonella and then boosted intranasally with Ag85B-ESAT6/LTK63 led to a significant increase in protection, equivalent to that observed in mice vaccinated with BCG. In a separate study, flow cytometry and confocal microscopy were used to examine the frequencies and localisation of innate immune cells, their activation status, as well as the expression of cell adhesion molecules following intranasal immunisation. I found striking differences between the cell surface phenotype of leukocytes and their pattern of distribution in the tissues examined at all time points tested after immunisation. Following on from these results one particular cell type was examined in more depth to determine its role in adaptive immune responses.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available