Immunological biomarkers of protection against tuberculosis
I am is interested in understanding which immune response elements are responsible for protection against infection with Mycobacterium tuberculosis, the causative agent of TB, as well as those which prevent the development of active TB disease.
Although it provides incomplete protection against TB, there is much to be learnt from the immune response to the BCG vaccine which in certain circumstances, may be effective. Although traditionally seen as T-cell-mediated, recent times have seen an increased interested in the role of B-cells and antibodies as well as potentially long-lived innate cells in immune protection against TB. As BCG is known to impact upon each of these immune compartments, each or all could have a role in protection.
In collaboration with teams at the MRC/UVRI & LSHTM Unit in Uganda, the International Tuberculosis Research Center, Korea and Institut Politecnico Nacional, Mexico, I use samples from BCG-vaccinated individuals, a variety of in vitro cellular models of innate and adaptive immune responses and analytical methods such as functional bacterial inhibition assays, multiparameter flow cytomtry, ELISA/Luminex and DNA methylation analysis to probe questions such as:
- the phenotype and function of BCG-vaccine-induced T-cells
- the potential for BCG-"trained" monocytes to protect against TB
- the role of metabolic intermediates in BCG-induced trained immunity and the potential for these to enhance vaccine effectiveness
- the use of immunological biomarker assays to monitor responses in patients and in vaccine trials against TB in different settings