title: The influence of bacille Calmette-Guerin vaccine strain on the immune response against tuberculosis: a randomized trial.
abstract: BACKGROUND
  Approximately 100 million doses of bacille Calmette-Guérin (BCG) vaccine are given each year to protect against tuberculosis (TB). More than 20 genetically distinct BCG vaccine strains are in use worldwide. Previous studies suggest that BCG vaccine strain influences the immune response and protection against TB. Current data on which BCG vaccine strain induces the optimal immune response in humans are insufficient.
  
  
  OBJECTIVE
  To compare the immune response to three different BCG vaccine strains given to infants at birth.
  
  
  METHODS
  Newborn infants in a tertiary women's hospital were immunized at birth with one of three BCG vaccine strains. A stratified randomization according to the mother's region of birth was used.
  
  
  RESULTS
  The presence of mycobacterial-specific polyfunctional CD4 T cells measured by flow cytometry 10 weeks after immunization. Of the 209 infants immunized, data from 164 infants were included in the final analysis (BCG-Denmark, n = 54; BCG-Japan, n = 54; BCG-Russia, n = 57). The proportion of polyfunctional CD4 T cells was significantly higher in infants immunized with BCG-Denmark (0.013%) or BCG-Japan (0.016%) than with BCG-Russia (0.007%) (P = 0.018 and P = 0.003, respectively). Infants immunized with BCG-Japan had higher concentrations of secreted Th1 cytokines; infants immunized with BCG-Denmark had higher proportions of CD107-expressing cytotoxic CD4 T cells.
  
  
  CONCLUSIONS
  There are significant differences in the immune response induced by different BCG vaccine strains in newborn infants. Immunization with BCG-Denmark or BCG-Japan induced higher frequencies of mycobacterial-specific polyfunctional and cytotoxic T cells and higher concentrations of Th1 cytokines. These findings have potentially important implications for global antituberculosis immunization policies and future tuberculosis vaccine trials.
authors.affiliation: Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ritz
authors.forename: Binita
authors.initials: B
authors.lastname: Dutta
authors.forename: Susan
authors.initials: S
authors.lastname: Donath
authors.forename: Dan
authors.initials: D
authors.lastname: Casalaz
authors.forename: Tom G
authors.initials: TG
authors.lastname: Connell
authors.forename: Marc
authors.initials: M
authors.lastname: Tebruegge
authors.forename: Roy
authors.initials: R
authors.lastname: Robins-Browne
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.forename: Warwick J
authors.initials: WJ
authors.lastname: Britton
authors.forename: Nigel
authors.initials: N
authors.lastname: Curtis
mesh_terms: D000465:Algorithms; D001315:Australia; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D003718:Denmark; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006771:Hospitals, Maternity; D006785:Hospitals, University; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D017410:Practice Guidelines as Topic; D012426:Russia; D012494:Sampling Studies; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology; D014611:Vaccination / Q000592:standards
chemical_list: D001500:BCG Vaccine; D015415:Biomarkers; D016207:Cytokines; D032581:Tuberculosis Vaccines