Dr Monika Looney, SATVI, Cape Town University, South Africa - VALIDATE Fellow
Pilot study to investigate tissue-based immunological profiles associated with TB with single-cell spatial resolution in human lymph nodes
Project Aims
New, effective, vaccines for the prevention tuberculosis (TB) are desperately needed. Novel vaccine candidates are showing promise, but the highest level of protection demonstrated to date is still only ~50% with the M72:AS01E TB vaccine. While this level of efficacy represents a major achievement in the field, ideally, we would like to develop vaccines that are able to prevent TB disease in more individuals.
To do so, we must improve our understanding of what happens in lymph nodes, where vaccine-mediated protective responses are initiated. However, because lymph nodes are not easily accessible, they have been left out of many vaccine research studies which favour investigation of alternative sample types, like blood.
While many important findings about vaccine responses have been discovered using blood, this technique provides an indirect, incomplete picture of what kinds of responses are being generated, given that it only allows analysis of immunological features that circulate, whereas many important features may remain localized to the lymph node. This limits our ability to design more effective vaccines.
Our long-term goal is to investigate immune responses to Mtb in human lymph nodes following vaccination. This will be a major undertaking with many stages, so as a first step, we propose this small pilot study that will enable us to evaluate our ability to characterize the structurally preserved immune environment of human lymph nodes from individuals with Mtb infection. This pilot will not directly involve a vaccine angle but will provide the strong foundation of preliminary research that is required for building a larger scale vaccine study.
For this pilot, we aim to do the following:
1) Investigate transcriptional immune profiles in lymph nodes from individuals with TB
collected via fine needle aspiration.
2) Characterize the spatial immune architecture in whole lymph node sections from
individuals with TB.
Find out more about Dr Monika Looney here.
