Determining the metabolic impact of BCG vaccination
Led by Dr Mrinal Kumar Das (University of Leicester, United Kingdom), with Dr Simone Joosten (University Leiden, Netherlands).
Project Aim
For more than 100 years, BCG vaccination has been used to protect against tuberculosis (TB). While BCG is being used to immunise millions of children every year, it is not as protective as other childhood vaccinations, and its effect wanes with minimal protection against pulmonary disease in adults. Other potential TB vaccine candidates have been developed but none of them has reached the final stage of replacing BCG. BCG also delivers non-TB related protection, and we need to understand how this occurs to improve on BCG while maintaining its current efficacy. A limitation of TB vaccine development is our inability to predict success against TB. Recent efforts in improving on the efficacy of BCG have involved the manipulation of the BCG bacteria and delivery of standard BCG by alternate routes. These strategies have been assessed for their ability to alter immunological parameters but are not screened for their ability to impact broader health consequences of BCG vaccination. Our recent published work has shown that immune signals in the liver alter overall metabolism during TB. Following this observation, we have investigated how the liver behaves when the TB infected subject has been BCG vaccinated – and we have measured an impact. In this project, we will define how BCG vaccination alters the liver response both directly and following TB infection and how these changes impact the health of the subject. Future research work on new vaccine candidates will be informed by our studies and we hope to develop markers of immune responsiveness to vaccination that will correlate with a healthy holistic response to infection in terms of both reduced bacterial burden but also improved capacity to accommodate infection with a balanced metabolic response.
