Cytokine responses to both CT99021 mouse mycobacteria-specific (cCFP and Ag85) and non-specific stimuli (TT and
PHA) differed between BCG strains (Table 2). In particular, the BCG-Denmark group demonstrated IFN-γ responses that were significantly higher than those of the BCG-Russia group to all four stimuli, as well as higher IL-13 responses to cCFP and PHA. Compared to BCG-Russia, IL-5 responses did not differ in the BCG-Denmark group. However in the BCG-Bulgaria group, they were marginally lower in response to specific antigens. IL-10 levels were notably higher for both BCG-Bulgaria and BCG-Denmark groups relative to BCG-Russia in response to all stimuli. Overall, 59.0% selleck of the one-year olds had a BCG scar. There were significant differences between the proportions of each group who had a BCG scar: BCG-Denmark had a markedly higher association with scarring than BCG-Russia or BCG-Bulgaria (p < 0.001; Table 2). BCG scar size did not significantly differ between groups (data not shown). The above observations were similar after stratifying by infant sex. For cCFP, Ag85 and PHA there was a tendency for some effects of BCG strain to appear stronger in female infants (data not shown). In response to TT, there was an interaction between sex
and strain for IL-10 responses (Table 3), with stronger associations amongst female before infants. However, similar proportions of girls and boys developed a scar. Samples from infants with BCG scars demonstrated higher IFN-γ and IL-13 responses to mycobacterial antigens, but not to TT or PHA, than those without a scar (Table 4). There were no differences in IL-5 or IL-10 responses by scar status for any stimulus. BCG-related adverse events included 2 ulcers and 12 abscesses,
occurring in 0.3% of the BCG-Russia group, 1.0% of the BCG-Bulgaria group and 1.8% of the BCG-Denmark group (p = 0.025). Observed mortality appeared slightly higher in the BCG-Denmark group, however the study was underpowered to detect significant differences ( Table 5). This infant cohort in a low-resource tropical country, recruited before birth and followed up prospectively, provided a good opportunity to investigate potential differences between the effects of three BCG strains that are commonly used globally. We found significant differences in mycobacteria-specific and non-specific immune responses, and in the frequency of BCG-associated adverse events, according to the vaccine strain used. To our knowledge, this is the largest study to evaluate the effects of BCG strain on immune responses to the BCG vaccine and the only study to assess both specific and non-specific responses [11]. Other studies have shown that BCG elicits type 1 and type 2 responses, to both mycobacteria-specific and non-specific stimuli [28] and [29].