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

Summary 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. This includes reducing all cause infant mortality, likely by protecting against non-mycobacterial infectious diseases. The protection is proposed to result from the immunomodulatory 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. This includes reducing all cause infant mortality, likely by protecting against non-mycobacterial infectious diseases. The protection is proposed to result from the immunomodulatory effects of BCG.

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

• The BRACE trial: our international RCT of nearly 7000 healthcare workers across 34 sites in five countries. This trial is working to determine if BCG vaccination reduces the impact of COVID-19 and other respiratory 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.

Using samples from these trials we have previously shown that neonatal BCG vaccination reduces cytokine responses to a range of pathogens (MIS BAIR) and adult BCG vaccination results cytokine but increased T cell responses to SARS-CoV-2 (BRACE).

You will use samples from participants in one or both of these clinical trials to help characterise BCG-induced changes in the immune system and the underlying mechanism of action. In this project you will have the opportunity to use a combination of analysis techniques to investigate the immune system such as in vitro stimulation, single cell RNA sequencing, flow cytometry and more.

The findings of this project will provide important insights into the immunomodulatory effects of BCG and the associations between these changes as well as the beneficial clinical effects of this 100-year-old vaccine.

The Infectious Diseases Laboratory is located at the Murdoch Children's Research Institute, part of the Melbourne Children's Campus, which also includes the Royal Children's Hospital and the University of Melbourne.