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Title: Impact of S. aureus colonisation in human & mouse populations and relationship to vaccination
Author: Flaxman, Amy
ISNI:       0000 0004 7229 6189
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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Staphylococcus aureus (S. aureus) is both a commensal and a pathogenic Gram-positive bacterium. Approximately one third of the adult population are asymptomatic nasal carriers of S. aureus. Clinical staphylococcal disease can range from skin and soft tissue infections to bacteraemia, often caused by the carriage strain. For this reason, interventions which reduce colonisation should reduce the mortality and morbidity of disease, something which has been proved using antimicrobial decolonisation. An alternative approach to doing this is through vaccination. However, to date, vaccines against S. aureus in clinical trials have been unsuccessful, their failure highlighting our lack of understanding of the interactions between the bacterium and the host in both carriage and infection situations. While human carriage studies and animal experimental models are both useful for dissecting out such interactions, the latter represent a platform in which to test pre-clinical vaccine candidates against colonisation. In this thesis I have investigated the relationship between S. aureus colonisation and immune responses against the organism. I have done this both in a human cohort study in a unique confined population, and in a murine model. I present evidence that interactions between S. aureus and other species within the microbiome can influence magnitude of immune responses in humans in a confined environment. I have established a novel, long-term murine S. aureus gastrointestinal (GI) tract model which is needle-free and does not require antibiotics. I used this model to investigate immune phenotype of colonisation and to assess efficacy of S. aureus vaccine candidates in reducing colonisation. I identified a vaccine candidate which, when administered prophylactically, can reduce subsequent experimental S. aureus colonisation in mice. Through studies of both human and murine colonisation, this thesis increases our understanding of the host-bacterium relationship during colonisation. A new colonisation model is now available for testing vaccines and one vaccine candidate deserves further investigation.
Supervisor: Wyllie, David ; Klenerman, Paul Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available