Patterns and implications of naturally acquired immune responses to environmental and tuberculous mycobacterial antigens in northern Malawi

Interferon (IFN)-gamma responsiveness to 12 purified protein derivative (PP D) and new tuberculin antigens from 9 species of mycobacteria was assessed, using a whole blood assay, in 616 young adults living in northern Malawi, where Mycobacterium bovis bacille Calmette-Guerin (BCG) vaccination provide s no protection against pulmonary tuberculosis. The prevalence of IFN-gamma responsiveness was highest for PPDs of M. avium, M. intracellulare, and M. scrofulaceum (the MAIS complex). Correlations between responsiveness paral leled genetic relatedness of the mycobacterial species. A randomized, contr olled trial was carried out, to assess the increase in IFN-gamma responsive ness to M. tuberculosis PPD that can be attributed to M. bovis BCG vaccinat ion. The BCG-attributable increase in IFN-gamma response to M. tuberculosis PPD was greater for individuals with low initial responsiveness to MAIS an tigens than for those with high initial responsiveness. Although not statis tically significant, the trend is consistent with the hypothesis that prior exposure to environmental mycobacteria interferes with immune responses to BCG vaccination.