Project Title

Characterization of innate and adaptive immune responses to mycobacterial antigens in household contacts of Tuberculosis patients.

EDCTP Project Call

Career Development Fellowship (CDF)

Project Objectives

1. To assess differences in the frequency and phenotype of immune cells responding to mycobacterial stimulation in LTBI and IGRA negative contacts of TB patients and unexposed healthy community controls. 2. Establish the mycobacterial growth inhibition assay (MGIA) at AHRI using both whole blood and PBMC. 3. Evaluate correlation between immune responses to mycobacterial stimulation with the ability to inhibit mycobacterial growth in a functional in-vitro assay. 4. Investigate correlations between epigenetic modifications in innate immune cells and trained immunity in IGRA negative house hold contacts.

Study Design

Cross-sectional study

Project Summary

Tuberculosis (TB) continues to cause morbidity and mortality to millions each year. A vaccine is essential to control the epidemic; however, vaccine development is hindered by the lack of biomarkers that correlate with protection and vaccine efficacy. To identify new biomarkers, we need to understand the host immune responses during exposure, infection and disease. In this study, we aim to characterize innate immune responses and IFN independent adaptive immune responses in TB exposed individuals, focusing on individuals who remain IGRA negative despite continuous exposure to TB, known as ‘Resisters’. We will look at differences in immune responses to TB among different groups of exposed, and unexposed individuals. We will evaluate the ability of immune cells to inhibit mycobacterial growth using a functional in-vitro assay and correlate the findings with the types of immune responses involved and epigenetic modifications of innate immune cells. We have enrolled study participants, collected the necessary specimen and stored them. The IGRA test was performed to group exposed individuals into latent TB infected (LTBI) or Resister category. Immune responses to TB antigen were measured using Luminex assay and ELISA. The main finding so far is that Resisters show a difference in selected cytokine immune response while having a comparable antibody response. However, the antibody response in resisters is comparable to LTBI participants.

Host Organisation

Current Organisation

University of Oxford

Current Job Title

Postdoctoral Scientist

Biography