Impact of S. aureus colonisation in human & mouse populations and relationship to vaccination
<p><em>Staphylococcus aureus (S. aureus)</em> is both a commensal and a pathogenic Gram-positive bacterium. Approximately one third of the adult population are asymptomatic nasal carriers of <em>S. aureus</em>. Clinical staphylococcal disease can range from skin and sof...
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2017
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| _version_ | 1826282148528652288 |
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| author | Flaxman, A |
| author2 | Wyllie, D |
| author_facet | Wyllie, D Flaxman, A |
| author_sort | Flaxman, A |
| collection | OXFORD |
| description | <p><em>Staphylococcus aureus (S. aureus)</em> is both a commensal and a pathogenic Gram-positive bacterium. Approximately one third of the adult population are asymptomatic nasal carriers of <em>S. aureus</em>. 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 <em>S. aureus</em> 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.</p> <p>In this thesis I have investigated the relationship between <em>S. aureus</em> 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 <em>S. aureus</em> 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 <em>S. aureus</em> 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 <em>S. aureus</em> vaccine candidates in reducing colonisation. I identified a vaccine candidate which, when administered prophylactically, can reduce subsequent experimental <em>S. aureus</em> colonisation in mice.</p> <p>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.</p> |
| first_indexed | 2024-03-07T00:39:28Z |
| format | Thesis |
| id | oxford-uuid:828b07d4-1239-447d-b520-43c7491c03b7 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T00:39:28Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | oxford-uuid:828b07d4-1239-447d-b520-43c7491c03b72022-03-26T21:38:09ZImpact of S. aureus colonisation in human & mouse populations and relationship to vaccinationThesishttp://purl.org/coar/resource_type/c_db06uuid:828b07d4-1239-447d-b520-43c7491c03b7ORA Deposit2017Flaxman, AWyllie, DKlenerman, P<p><em>Staphylococcus aureus (S. aureus)</em> is both a commensal and a pathogenic Gram-positive bacterium. Approximately one third of the adult population are asymptomatic nasal carriers of <em>S. aureus</em>. 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 <em>S. aureus</em> 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.</p> <p>In this thesis I have investigated the relationship between <em>S. aureus</em> 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 <em>S. aureus</em> 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 <em>S. aureus</em> 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 <em>S. aureus</em> vaccine candidates in reducing colonisation. I identified a vaccine candidate which, when administered prophylactically, can reduce subsequent experimental <em>S. aureus</em> colonisation in mice.</p> <p>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.</p> |
| spellingShingle | Flaxman, A Impact of S. aureus colonisation in human & mouse populations and relationship to vaccination |
| title | Impact of S. aureus colonisation in human & mouse populations and relationship to vaccination |
| title_full | Impact of S. aureus colonisation in human & mouse populations and relationship to vaccination |
| title_fullStr | Impact of S. aureus colonisation in human & mouse populations and relationship to vaccination |
| title_full_unstemmed | Impact of S. aureus colonisation in human & mouse populations and relationship to vaccination |
| title_short | Impact of S. aureus colonisation in human & mouse populations and relationship to vaccination |
| title_sort | impact of s aureus colonisation in human amp mouse populations and relationship to vaccination |
| work_keys_str_mv | AT flaxmana impactofsaureuscolonisationinhumanampmousepopulationsandrelationshiptovaccination |