Metabolic reprogramming for improved BCG vaccine efficacy

Cellular metabolism and immunity are inextricably linked. In this project we are investigating the hypothesis that the BCG vaccine, which works with variable efficacy across the globe, will confer more effective protection against tuberculosis if delivered to cells that are metabolically optimal in terms of their immune capabilities.

Having previously demonstrated a fumarate-induced mitochondrial signature of trained innate immunity in monocytes, we are now exploring the potential of using metabolites such as fumarate to re-programme cells at the site of vaccination for better responses to BCG.

Using both in vitro models of human cellular immune responses and murine vaccination models, we are delivering metabolites to monocytes isolated from human blood or to the skin site of vaccination respectively, before vaccinating with BCG. We are then testing for immunological markers of vaccine response as well as investigating the change in metabolic pathway usage of immune cells as a result of metabolite treatment.

Novel approaches to optimize vaccine-delivered immune protection can help deliver an effective vaccine against tuberculosis, which currently kills more people worldwide than any other infectious disease. There is also potential for a wider impact on the development of vaccines for other infectious disease threats, for example SARS-CoV-2.