The BCG in situ study – novel techniques applied to a 100-year-old vaccine

The use of Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) spans more than a century. Besides protection against severe paediatric TB, randomized trials and novel advances within innate immunology documented that BCG has beneficial non-specific effects, providing protection against non-TB infections. Since paediatric intradermal BCG vaccination has proved unable to contain adult pulmonary tuberculosis, several novel TB vaccines are under development, most of which build upon BCG. BCG's status as an essential remedy against TB will therefore be maintained, but despite many decades of near-universal intradermal use, the local responses to BCG in the skin have not been thoroughly elucidated. We therefore developed appropriate methods to capture the localised skin events at the cellular and molecular level after intradermal BCG vaccination. This work informs future studies to identify the immunological events induced following administration of BCG to accelerate development of improved or new vaccines against <i>Mycobacterium tuberculosis (Mtb)</i>. We employed advanced technologies such as spatial transcriptomics on skin tissue punch biopsies and cell-free plasma transcriptomics (liquid biopsies) to characterize both the local (<i>in situ</i>) skin and systemic (peripheral blood) response to BCG via:•Whole blood transcriptomics and epigenetic analysis•Blood immune cell characterization•Plasma proteomic and metabolomic analysis.