title: Immune responses to mycobacterial antigens in the Gambian population: implications for vaccines and immunodiagnostic test design.
abstract: Recombinant immunodominant mycobacterial antigens are needed for the development of new vaccines and immunodiagnostic tools for use against tuberculosis. Ubiquitous exposure to mycobacteria in tropical countries could influence vaccine-induced immunity and the specificity of tuberculosis immunodiagnosis. For this study conducted in The Gambia, cellular immune responses to recombinant mycobacterial antigens were characterized in Mycobacterium bovis BCG-vaccinated and nonvaccinated infants, adult community controls, household contacts, health care workers, and tuberculosis patients. Neonatal BCG vaccination induced gamma interferon (IFN-gamma) responses to Mtb8.4, Mtb32-C, Mtb39A, Mtb9.9A, and Mtb32-N, but not CFP-10 (Mtb11) and alpha-crystallin (Mtb16). Exposure to Mycobacterium tuberculosis in household contacts and health care workers was associated with high responses to CFP-10 and alpha-crystallin. Generally, low IFN-gamma responses were found in tuberculosis patients. These results suggest that Mtb8.4, Mtb32-C, Mtb39A, Mtb9.9A, and Mtb32-N may be used in a subunit vaccine to boost BCG-induced immunity. While CFP-10 and alpha-crystallin are promising candidates for the immunodiagnosis of M. tuberculosis infection or for vaccine use, disease-associated immunosuppression may prevent IFN-gamma immunodiagnosis of more advanced tuberculosis.
authors.affiliation: Medical Research Council Laboratories, Fajara, The Gambia. Johan.Vekemans@ulb.ac.be
authors.forename: Johan
authors.initials: J
authors.lastname: Vekemans
authors.forename: Martin O C
authors.initials: MO
authors.lastname: Ota
authors.forename: Jackson
authors.initials: J
authors.lastname: Sillah
authors.forename: Katherine
authors.initials: K
authors.lastname: Fielding
authors.forename: Mark R
authors.initials: MR
authors.lastname: Alderson
authors.forename: Yasir A W
authors.initials: YA
authors.lastname: Skeiky
authors.forename: Wilfried
authors.initials: W
authors.lastname: Dalemans
authors.forename: Keith P W J
authors.initials: KP
authors.lastname: McAdam
authors.forename: Christian
authors.initials: C
authors.lastname: Lienhardt
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marchant
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D019353:Endemic Diseases; D005714:Gambia / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D009161:Mycobacterium / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; D011994:Recombinant Proteins; D007371:Interferon-gamma