Trained immunity: using controlled human infection to study non-specific beneficial effects of vaccination

Vaccines can train the immune system to fight off infections they were never designed to target. This project will use controlled human infection—deliberately exposing volunteers to a pathogen under carefully monitored conditions—to study how and why this happens. The problem is that current vaccines are designed to protect against a single disease, but real-world evidence suggests some vaccines also reduce deaths and hospitalisations from unrelated infections. No one fully understands the biological mechanisms behind this “trained immunity,” which means we cannot deliberately design vaccines to maximise these broader benefits. If this research succeeds, it could lead to new vaccine adjuvants—ingredients that boost immune responses—and optimised vaccination schedules that provide both specific protection and general immune strengthening. That could reduce the overall burden of infectious disease, particularly in populations vulnerable to multiple pathogens. This is fundamental science. It will not produce a market-ready vaccine or adjuvant within the grant period. But understanding how the immune system retains a memory of past infections and vaccinations could eventually reshape how we design immunisation programmes, especially against respiratory viruses and bacteria that cause pneumonia and sepsis.