T cell receptor sequencing to identify correlates of protection in human tuberculosis vaccine studies
Led by Dr Gabriele Pollara (UCL, UK), with Prof Mahdad Noursadeghi (UCL, UK), Assoc Prof Susanna Brighenti (Karolinska Institutet, Sweden), Assoc Prof Senait Ashenafi (Addis Ababa University, Ethiopia) and Prof Benny Chain (UCL, UK)
Project Aims
Tuberculosis (TB) is the disease caused by infection with Mycobacterium tuberculosis (Mtb). TB is the most common infectious cause of death world-wide. BCG vaccination against TB, is partially effective in children but does not provide long lasting protection for adults, who are most frequently affected. A critical barrier to the development of better vaccines is the lack of laboratory measurements that predict how well new vaccine candidates will work. In fact, we do not know precisely how the immune system protects us against TB. We aim to identify new measurements of immune protection against TB, which may be used to develop and test new vaccines in the future.
We do know that immune cells called T cells make an important contribution to protection against TB. These are families of cells which recognise and respond to certain molecules within the bacteria. Simply measuring the number of T cells that recognise Mtb in blood samples has not provided a good measure of vaccine protection. We propose that measuring the number of distinct families of T cells at the site of infection may be more informative. In this project, we aim to show proof of principle that these measurements can be made at the site of a skin test which stimulates an immune response to Mtb, and that the distinct T cell families which accumulate in the skin test are more similar to the site of disease than in blood samples. Importantly, our approach to measure different families of T cells at the site of an immune response within people, can be applied in large scale clinical studies, first to validate these measurements as predicting immune protection against TB and second to test the effects of vaccination.
Project Outcomes
Tuberculosis (TB) is the disease caused by infection with Mycobacterium tuberculosis (Mtb). TB is the most common infectious cause of death world-wide. BCG vaccination against TB, is partially effective in children but does not provide long lasting protection for adults, who are most frequently affected. A critical barrier to the development of better vaccines is the lack of laboratory measurements that predict how well new vaccine candidates will work. In fact, we do not know precisely how the immune system protects us against TB. The project aimed to identify new measurements of immune protection against TB, which may be used to develop and test new vaccines in the future.
We do know that immune cells called T cells make an important contribution to protection against TB. These are families of cells which recognise and respond to certain molecules within the bacteria. Simply measuring the number of T cells that recognise Mtb in blood samples has not provided a good measure of vaccine protection. The project proposed that measuring the number of distinct families of T cells at the site of infection may be more informative. We aimed to show proof of principle that these measurements can be made at the site of a skin test which stimulates an immune response to Mtb, and that the distinct T cell families which accumulate in the skin test are more similar to the site of disease than in blood samples.
We have collected all the tissue and blood samples required for this project and extracted materials required for the assessment of the T cell families present. Analysis of our data is still ongoing, and we will share our findings as soon as possible. Our overall ambition remains to apply this assessment of T cells at the site of an immune response in large scale clinical studies to predict immune protection against TB and to test the effects of vaccination.
