Characterising control of mycobacterial growth in patients with TB disease and M. tuberculosis infection. (360G-Wellcome-103420_Z_13_Z)
TB can be viewed as a continuous spectrum extending from sterilising immunity, quiescent M. tuberculosis (M.tb) infection, and active disease. Identifying phenotypic subgroups within this spectrum is challenging and the tools we use are currently imperfect. An understanding of protective immunity against TB disease is lacking, as are predictors of risk of disease progression, biomarkers of responses to therapy and correlates of vaccine-induced protection. Mycobacterial growth inhibition assays offer a functional in-vitro evaluation of an individual's capacity to control mycobacterial growth. Preliminary data indicate that individuals with active disease exhibit greater control of mycobacterial growth that those with latent M.tb infection. My hypothesis is that this is related to the bacillary load experienced by the individual, akin to the spectrum of responses observed in another mycobacterial disease (leprosy). Humoral immune responses may contribute to the spectrum of M.tb infect ion (as in leprosy). I propose to study three populations of HIV-negative adults: a group with latent M.tb infection, a group with active pulmonary disease; a group of healthy, BCG-vaccinated and -na ve, controls. Associations between clinical phenotype, functional assay and B and T cell-associated immune signatures (by flow cytometry and gene expression) may help identify correlates of protective immunity and valuable host biomarkers.
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Grant Details
Amount Awarded | 61154 |
Applicant Surname | O'Shea |
Approval Committee | Clinical Interview Committee |
Award Date | 2014-02-18T00:00:00+00:00 |
Financial Year | 2013/14 |
Grant Programme: Title | Research Training Fellowship |
Internal ID | 103420/Z/13/Z |
Lead Applicant | Dr Matthew O'Shea |
Partnership Value | 61154 |
Planned Dates: End Date | 2016-03-31T00:00:00+00:00 |
Planned Dates: Start Date | 2014-04-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | South East |
Sponsor(s) | Prof Adrian Hill |