title: Comparison of IFN-gamma responses to mycobacterial antigens as markers of response to BCG vaccination.
abstract: An increase in interferon-gamma (IFN-gamma) production to Mycobacterium tuberculosis purified protein derivative (Mtb PPD), as measured in the cultured diluted whole blood assay, is one indicator of a protective immune response to BCG vaccine. We have explored the potential for this assay to be improved by measuring IFN-gamma responses to more defined antigens of M. tuberculosis (short-term and mid-term culture filtrates, ESAT-6, 38 kDa), Mycobacterium bovis (MPB70), M. bovis BCG (Antigen 85) and Mycobacterium leprae (35 kDa), in UK teenagers before and 1 year after BCG vaccination (or no vaccination as controls). There was a significant increase in response to the culture filtrates post-vaccination, but this was no greater than that to Mtb PPD. Many teenagers responded to the purified antigens, in particular to Antigen 85, prior to vaccination, and BCG vaccination could only augment this pre-existing response to a limited extent; prior exposure to environmental mycobacteria can thus induce cross-reactive responses to antigens which complicate interpretation of in vitro assays of vaccine response. In contrast, ESAT-6 was recognised by only one teenager prior to vaccination, and, as expected, responses were not boosted by BCG. We therefore conclude that Mtb PPD is the antigen preparation of choice for assessing the immunogenicity of BCG vaccination.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Weir
authors.forename: Paul E M
authors.initials: PE
authors.lastname: Fine
authors.forename: Sian
authors.initials: S
authors.lastname: Floyd
authors.forename: Sally
authors.initials: S
authors.lastname: Stenson
authors.forename: Carolynne
authors.initials: C
authors.lastname: Stanley
authors.forename: Keith
authors.initials: K
authors.lastname: Branson
authors.forename: Warwick J
authors.initials: WJ
authors.lastname: Britton
authors.forename: Kris
authors.initials: K
authors.lastname: Huygen
authors.forename: Mahavir
authors.initials: M
authors.lastname: Singh
authors.forename: Gillian
authors.initials: G
authors.lastname: Black
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Dockrell
mesh_terms: D000293:Adolescent; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D009161:Mycobacterium / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D014611:Vaccination
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D015415:Biomarkers; D007371:Interferon-gamma