Dr Paula Niewold, Leiden University Medical Center (LUMC), Netherlands - VALIDATE Fellow
Translating protective immune signatures in the lung to peripheral biomarkers for TB
Project Aims
Tuberculosis is an infectious disease primarily of the lung, caused by Mycobacterium tuberculosis. It can spread between people via coughing and yearly 10 million people become infected, with 1.5 million people dying as a result of infection, particularly in low and middle income countries. Treatment consists of multiple months of antibiotics, but is becoming less effective as antibiotic resistance increases. Furthermore, the only approved vaccine, BCG, has limited efficacy. Ongoing attempts to develop improved vaccines are hampered by a lack of knowledge on the characteristics of an effective immune response against Mycobacterium tuberculosis. In this project, we aim to identify immune responses that are protective against Mycobacterium tuberculosis.
Non-human primates are an important and representative model for human infection with Mycobacterium tuberculosis as they have an immune system and disease presentation very similar to humans. In this model, we identified cells in the lung that work together to reduce disease severity. In this project, I will use state of the art technology to characterize these cells in detail to learn more about how they contribute to limiting TB disease. Next, I will translate the characteristics of these protective immune cells to a signature based on proteins they express, which can be detected by routine diagnostics techniques. Using such techniques, I will look for a corresponding population in the blood and translate this to humans. This will allow us to detect these protection-associated cells in the blood of humans that have been vaccinated or infected, and potentially predict whether they are protected from disease or not. This is valuable for diagnostics as well as early assessment of vaccine efficacy. The knowledge gained here about immune responses against TB are likely to contribute to improved vaccine design to achieve better protection against Mycobacterium tuberculosis infection and ultimately reduce the burden of tuberculosis.
Find out more about Dr Paula Niewold here.
