Tuberculosis, caused by infection with Mycobacterium tuberculosis (M.tb), remains a global health problem. Drug resistance and high rates of HIV infection have fuelled the pandemic and, although a vaccine exists, its ability to protect from pulmonary tuberculosis varies between 0 and 80%. Bacille Calmette Guerin (BCG) has been administered to billions worldwide yet its protective mechanisms remain unknown, as do the reasons for its failure to protect in many parts of the world. Modified Vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel candidate vaccine designed to boost immune responses to BCG and improve protection. An aim of this thesis has been to characterise the innate immune response to an MVA85A boosting vaccination in both UK adults and South African infants. In the former, volunteers develop a strong innate response following vaccination however this does not always translate into a robust adaptive response to antigen 85A (Ag85A), which is determined in part by Treg expansion and the nuclear protein HMGB1 signaling through the TLR1-2-6 axis. By contrast, not all South Africa infants mount a strong innate immune response to MVA85A yet this response is correlated with the magnitude of the adaptive response. The immune response to BCG in both populations is also characterised and an association found between increased production of IL-17, IL-22 and IFN-γ in response to BCG stimulation and control of mycobacterial growth. The results presented here further the knowledge on the links between innate and adaptive responses to vaccination with BCG and MVA85A and the variation in mechanisms involved in different populations.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:629562 |
| Date | January 2014 |
| Creators | Matsumiya, Magali Maya Laurence |
| Contributors | McShane, Helen; Hill, Adrian V. S. |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:bcec5004-fd34-4d36-b088-c0b7e31a87f8 |
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