Bacille Calmette-Guérin Skin Reaction Predicts Enhanced Mycobacteria-Specific T Cell Responses in Infants.

Scar formation following bacille Calmette-Guérin (BCG) vaccination has been associated with lower all-cause mortality; the relation between scar and mycobacterial-specific protection against tuberculosis is debated.To evaluate the association between BCG skin reaction and mycobacteria-specific immune responses.Post-hoc analysis on 214 infants in Australia randomised to vaccination with one of three BCG vaccine strains (BCG-Denmark, BCG-Japan or BCG-Russia) given at birth or BCG-Denmark given at two months of age.BCG skin reaction size and characteristics ten weeks after vaccination were related to the in-vitro mycobacterial-specific immune responses measured in stimulated whole blood.The size and characteristics of the skin reaction correlated positively with in-vitro immune responses, even after adjusting for BCG vaccine strain and age at vaccination. Specifically, the reaction size and characteristics correlated with the proportion of mycobacteria-specific polyfunctional CD4+ T cells following stimulation with BCG and PPD, and, to a lesser extent, following stimulation with Mycobacterium tuberculosis (MTB) or M. ulcerans. A similar correlation was observed with concentrations of IFN-γ, IL-2, TNF and IL-13 in the supernatant following stimulation with BCG, PPD and MTB, and to some degree for the proportions of mycobacteria-specific polyfunctional CD8+ T cells and CD107+ cytotoxic cells.BCG skin reaction correlated with the magnitude of mycobacteria-specific T cell responses. As T cell responses play a key role in defence against mycobacteria, the relationship between BCG scar formation and protection against tuberculosis should be revisited. This may also extend to the need for BCG re-vaccination in scar-negative individuals.