Defining the mechanisms that underpin the beneficial off-target effects of BCG

Summary Defining the mechanisms that underpin the beneficial off-target effects of BCG

Project Details

In addition to protecting against its target disease, tuberculosis, the Bacillus Calmette-Guérin (BCG) has beneficial off-target ('heterologous' or 'non-specific') effects on human health including reducing all cause infant mortality, likely by protecting against non-mycobacterial infectious diseases. This protection is proposed to result from the immunomodulatory effects of BCG.

Our team has established two randomised controlled trials (RCTs) investigating whether BCG protects against non-mycobacterial diseases:

• Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR): our RCT of neonatal BCG vaccination in >1200 children in Melbourne to determine if BCG protects against allergic disease, eczema, asthma and infections.
• The BRACE trial: our international RCT of >10,000 healthcare workers to determine if BCG vaccination reduces the impact of COVID-19 and other respiratory diseases.

This project will use samples from participants in one or both of these RCTs to characterise BCG-induced changes in the immune system. This project will use a combination of in vitro stimulation, flow cytometry, multiplex cytokine assays, epigenetic analysis and gene expression. The findings of this project will provide important insights into the immunomodulatory effects of BCG and the associations between these changes and the beneficial clinical effects of this vaccine.