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

Vaccines can make the immune system better at fighting off infections they were not designed to target. This project will use controlled human infection—deliberately exposing volunteers to a pathogen—to study how and why this happens. Most vaccines are designed to protect against a single disease, but evidence suggests they sometimes have broader, non-specific benefits. For example, some vaccines reduce deaths from unrelated infections. The mechanisms behind this “trained immunity” remain poorly understood. This research aims to fill that gap by examining how vaccination and infection alter the immune system’s baseline responsiveness to a range of clinically significant pathogens, including *Streptococcus pneumoniae*, tuberculosis, and respiratory viruses such as RSV and SARS. If successful, the work could lead to new adjuvant formulations that deliberately trigger broad immune benefits, and to optimised vaccine schedules that maximise these effects. That would improve how vaccines are designed and deployed globally, potentially reducing the burden of infectious diseases beyond the target pathogen. The project is fundamental science with clear translational potential—it seeks a mechanistic understanding of a real-world observation that could reshape vaccination strategy.