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Title: Evaluation of the non-specific effects of Bacille Calmette-Guérin (BCG) vaccination in healthy UK adults
Author: Wilkie, Morven Elizabeth Mary
ISNI:       0000 0004 7960 0657
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2019
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Tuberculosis is the leading single infectious disease killer in the world, and the global burden of LTBI and TB disease, with the addition of antimicrobial drug resistance means there is a desperate need for a safe and effective TB vaccine. BCG is the only licensed vaccine and extremely variable in efficacy. However, BCG potentially exerts a non-specific beneficial effect - protecting infants from other causes of death such as respiratory infections and fever. Data from randomised and observational studies in support have been variable in quality; however the WHO reviewed the data and concluded that the effect was likely real, but that more robust data was needed. The aim of this my study was to evaluate the potential non-specific effects of BCG using an in-vitro whole blood growth inhibition assay as a surrogate marker of an individual's ability to control growth of bacteria before and after vaccination with BCG. Identification of improved control of bacterial net growth following vaccination with BCG would provide evidence to support large, costly, randomised control trials in TB high burden countries. The assay did not demonstrate improved control of growth of four pathogens in the whole blood GIA following BCG vaccination and was subject to bacterial inoculum batch effect and other variables such as haemoglobin. A PBMC GIA potentially detected a subtle improvement in control of bacteria in the same volunteer cohort, but requires further optimisation. Volunteers who received BCG vaccination had an expected clinical and immunological reaction to vaccination with BCG. Pilot data exploring innate immune 'memory' through secondary antigenic stimulation of PBMCs did not demonstrate a significant increase in cytokine production, but numbers were small and more work is necessary.
Supervisor: McShane, Helen ; Wyllie, David Sponsor: Gates Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Vaccination