title: Novel human in vitro system for evaluating antimycobacterial vaccines.
abstract: Major research efforts are directed towards the development of a better antimycobacterial vaccine. But progress in the field of tuberculosis vaccine development has been hampered by the lack of human in vitro models to assess vaccine immunogenicity and efficacy. New candidate vaccines will have to be evaluated against the existing Mycobacterium bovis BCG "gold standard." It is therefore important to understand the type of immune responses elicited by BCG vaccination to enable comparisons with potential new candidates. We used a novel human in vitro whole-blood model, which measures immune responses to mycobacteria by use of reporter gene-tagged BCG (BCG lux), to study immune responses to BCG vaccination in 50 neonates in a setting in Cape Town, Republic of South Africa, where tuberculosis is endemic. BCG vaccination significantly reduced growth of BCG lux in whole blood (prevaccination median growth ratio [GR], 9.6; range, 1.3 to 24; postvaccination median GR, 3.9; range, 0.6 to 12.2 [P < 0.0001]). Growth of BCG lux was better restricted in vaccinated infants than in unvaccinated age-matched controls (n = 4). BCG vaccination induced significantly higher gamma interferon production in response to BCG lux (P < 0.0001) and to purified protein derivative (P = 0.0001). No significant changes in either growth of BCG lux or cytokine production occurred in an adult control group (n = 6) over the study period. The whole-blood luminescence model detects changes in cellular immune responses to mycobacteria induced by BCG vaccination. It is therefore a useful new tool in studying the immunogenicity of newly developed vaccine candidates prior to large field trials assessing efficacy.
authors.affiliation: School of Child and Adolescent Health, Red Cross Children's Hospital, University of Cape Town, Republic of South Africa. b.kampmann@imperial.ac.uk
authors.forename: Beate
authors.initials: B
authors.lastname: Kampmann
authors.forename: Gwen N
authors.initials: GN
authors.lastname: Tena
authors.forename: Shumikazi
authors.initials: S
authors.lastname: Mzazi
authors.forename: Brian
authors.initials: B
authors.lastname: Eley
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Young
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
mesh_terms: D001500:BCG Vaccine / Q000008:administration & dosage / Q000627:therapeutic use; D001769:Blood / Q000382:microbiology; D002986:Clinical Trials as Topic / Q000379:methods*; D017930:Genes, Reporter; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D008156:Luciferases / Q000235:genetics; D009163:Mycobacterium bovis / Q000235:genetics / Q000254:growth & development; D012107:Research Design; D013019:South Africa; D014374:Tuberculin Test; D014376:Tuberculosis / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology* / Q000592:standards; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma; D008156:Luciferases