Characterising control of mycobacterial growth in patients with TB disease and M. tuberculosis infection. (360G-Wellcome-103420_Z_13_Z)

£61,154

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