title: Gamma interferon responses induced by a panel of recombinant and purified mycobacterial antigens in healthy, non-mycobacterium bovis BCG-vaccinated Malawian young adults.
abstract: We have previously shown that young adults living in a rural area of northern Malawi showed greater gamma interferon (IFN-gamma) responses to purified protein derivatives (PPD) prepared from environmental mycobacteria than to PPD from Mycobacterium 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 from M. tuberculosis (38 kDa, MPT64, and ESAT-6), M. bovis (MPB70), M. bovis BCG (Ag85), and M. leprae (65 kDa, 35 kDa, and 18 kDa) in >600 non-M. bovis BCG-vaccinated young adults in the Karonga District of northern Malawi. IFN-gamma was measured by enzyme-linked immunosorbent assay (ELISA) in day 6 supernatants of diluted whole-blood cultures. The recombinant M. leprae 35-kDa and 18-kDa and purified native M. bovis BCG Ag85 antigens induced the highest percentages of responders, though both leprosy and bovine tuberculosis are now rare in this population. The M. tuberculosis antigens ESAT-6 and MPT64 and the M. bovis antigen 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 to M. tuberculosis PPD, Ag85, MPT64, and ESAT-6 but not to any of the leprosy antigens. We conclude that in this rural African population, exposure to M. tuberculosis or M. bovis is much less frequent than exposure to environmental mycobacteria such as M. avium, which have antigens homologous to the M. leprae 35-kDa and 18-kDa antigens. M. tuberculosis ESAT-6 showed the strongest association with the size of the Mantoux skin test induration, suggesting that among the three M. tuberculosis antigens tested it provided the best indication of exposure to, or infection with, M. tuberculosis.
authors.affiliation: Karonga Prevention Study, Chilumba, Malawi.
authors.forename: Gillian F
authors.initials: GF
authors.lastname: Black
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Weir
authors.forename: Steven D
authors.initials: SD
authors.lastname: Chaguluka
authors.forename: David
authors.initials: D
authors.lastname: Warndorff
authors.forename: Amelia C
authors.initials: AC
authors.lastname: Crampin
authors.forename: Lorren
authors.initials: L
authors.lastname: Mwaungulu
authors.forename: Lifted
authors.initials: L
authors.lastname: Sichali
authors.forename: Sian
authors.initials: S
authors.lastname: Floyd
authors.forename: Lyn
authors.initials: L
authors.lastname: Bliss
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jarman
authors.forename: Linda
authors.initials: L
authors.lastname: Donovan
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Warwick
authors.initials: W
authors.lastname: Britton
authors.forename: Glyn
authors.initials: G
authors.lastname: Hewinson
authors.forename: Kris
authors.initials: K
authors.lastname: Huygen
authors.forename: Jens
authors.initials: J
authors.lastname: Paulsen
authors.forename: Mahavir
authors.initials: M
authors.lastname: Singh
authors.forename: Ross
authors.initials: R
authors.lastname: Prestidge
authors.forename: Paul E M
authors.initials: PE
authors.lastname: Fine
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Dockrell
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D002648:Child; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007918:Leprosy / Q000453:epidemiology; D008295:Malawi / Q000453:epidemiology; D008297:Male; D009161:Mycobacterium / Q000235:genetics / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D009166:Mycobacterium leprae / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012424:Rural Population; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology; D014374:Tuberculin Test; D014376:Tuberculosis / Q000276:immunology; D014611:Vaccination
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma