Gamma Interferon Responses Induced by a Panel of Recombinant and Purified Mycobacterial Antigens in Healthy, Non-Mycobacterium bovisBCG-Vaccinated Malawian Young Adults

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Abstract
We have previously shown that young adults living in a rural area of northern Malawi showed greater gamma interferon (IFN-γ) responses to purified protein derivatives (PPD) prepared from environmental mycobacteria than to PPD fromMycobacterium tuberculosis. In order to define the mycobacterial species to which individuals living in a rural African population have been exposed and sensitized, we tested T-cell recognition of recombinant and purified antigens fromM. tuberculosis(38 kDa, MPT64, and ESAT-6),M. bovis(MPB70),M. bovisBCG (Ag85), andM. leprae(65 kDa, 35 kDa, and 18 kDa) in >600 non-M. bovisBCG-vaccinated young adults in the Karonga District of northern Malawi. IFN-γ was measured by enzyme-linked immunosorbent assay (ELISA) in day 6 supernatants of diluted whole-blood cultures. The recombinantM. leprae35-kDa and 18-kDa and purified nativeM. bovisBCG Ag85 antigens induced the highest percentages of responders, though both leprosy and bovine tuberculosis are now rare in this population. TheM. tuberculosisantigens ESAT-6 and MPT64 and theM. bovisantigen MPB70 induced the lowest percentages of responders. One of the subjects subsequently developed extrapulmonary tuberculosis; this individual had a 15-mm-diameter reaction to the Mantoux test and responded toM. tuberculosisPPD, Ag85, MPT64, and ESAT-6 but not to any of the leprosy antigens. We conclude that in this rural African population, exposure toM. tuberculosisorM. bovisis much less frequent than exposure to environmental mycobacteria such asM. avium, which have antigens homologous to theM. leprae35-kDa and 18-kDa antigens.M. tuberculosisESAT-6 showed the strongest association with the size of the Mantoux skin test induration, suggesting that among the threeM. tuberculosisantigens tested it provided the best indication of exposure to, or infection with,M. tuberculosis.