Professor EmeritusWarwick Britton

Project Opportunities

Title: What determines memory T cell responses following immunisation for tuberculosis?

Summary of opportunity:

This will provide excellent training in cellular immunisation and vaccine development against a major human pathogen

Opportunity synopsis:

Tuberculosis (TB) remains a huge health problem word-wide, and the development of more effective vaccines than the current BCG vaccine is crucial for the control of TB in the long-term. Effective vaccines must stimulate memory CD4 T cell responses and the decline in these responses is one factor in the reactivation of TB. We have shown that a number of vaccine vectors, including recombinant viruses expressing mycobacterial epitopes, stimulate CD4 and CD8 T cell responses. This project will examine whether M. tuberculosis-specific memory T cells generated by mucosal immunisation with recombinant viruses expressing a CD4 T cell epitope differ in phenotype, functional properties, epigenetic markers and protective capacity against M. tuberculosis to those induced to the same epitope by pulmonary M. tuberculosis infection or by BCG immunisation. During T cell differentiation, epigenetic changes occur at genetic loci for "master" transcription factors, cytokines and effector molecules. These epigenetic changes have generally been characterised using in vitro differentiation of T cells, but more recent studies have been examined these changes during in vivo viral infections. We shall be comparing epigenetic changes at the sites for transcription factors and cytokines in CD4 T cells during M. tuberculosis and virus infections and BCG immunisation. This will assist in developing subunit TB vaccines that stimulate memory T cell responses against TB. This project will be undertaken in the Tuberculosis Research Program in the Centenary Institute