Differential productions of lipid virulence factors among BCG vaccine strains and implications on BCG safety

Safety of BCG is a major concern in countries with a high burden of HIV/AIDS. Current BCG vaccine comprises of a heterogeneous group of substrains showing genotypic differences. The impact of these differences on BCG efficacy and safety remains unknown. Here we show that three BCG substrains, BCG-Japan, -Moreau, and -Glaxo, do not produce phthiocerol dimycocerosates (PDIMs) and phenolic glycolipids (PGLs), two cell wall lipids known to be important for the virulence of Mycobacterium tuberculosis and Mycobacterium bovis, suggesting that these BCG strains are more attenuated than others. We found that there is a good correlation between the ability of BCG strains to produce these two lipids and the propensity of BCG to induce complications following vaccination in children, which provides a partial explanation for the molecular mechanisms of BCG reactogenicity. Our finding has important implications for national immunization programmes particularly in HIV endemic countries. We suggest that PDIMs/PGLs analysis could offer a practical means for assessing the safety of various BCG vaccine strains currently used in the world.