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Understanding immunity during TB exposure and the role of epigenetic modifications

                                                         

                                                           Source: https://rdcu.be/cl3YV (Nature Reviews Immunology)

Research Overview

Title: Characterization of innate and adaptive immune responses to mycobacterial antigens in household contacts of Tuberculosis patients (IRTBHHC)

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 IFNg 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 also include IGRA positive contacts as well as IGRA negative health community controls without exposure to TB. We will evaluate their ability 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.

The study will be done in Addis Ababa. Laboratory work will be done at AHRI. Various methods will be used to answer the study questions; including QuantiFeron TB Gold Assay, Intracellular Flowcytometry, Luminex assay, ELISA, Mycobacterial Growth Inhibition Assay (MGIA), and selected appropriate methods for epigenetic modifications (Histone modification and DNA Methylation). The expected outcomes include understanding of adaptive and in innate immunity, including trained immunity and the role of epigenetic modifications in resistance to infection.

Capacity Building

This project holds opportunity for various capacity building activities. The PI and co-investigators will be trained on methods of MGIA and epigenetic modifications. There will be knowledge transfer and these methods will be established at AHRI. Graduate students and research assistants will also be given training on flowcytometry, Luminex assay, and ELISA. Research ethics and GCP training will also be provided to health care professionals from the health centres in Addis Ababa.

Study Team

Supported by

This project is supported by AHRI, TBGEN-Africa (AAS/Wellcome Trust), EDCTP, OWSD-UNESCO, and NIH/ Fogarty International Center Global Infectious Diseases

This project is part of the EDCTP2 Programme supported by the European Union