title: Comparable CD4 and CD8 T cell responses and cytokine release after at-birth and delayed BCG immunisation in infants born in Australia.
abstract: More than 120 million doses of BCG vaccine are administered worldwide each year. Most infants are given BCG at birth in accordance with WHO recommendations. However, the effect of the maturing neonatal immune system on the immune response and protection conferred by BCG remains uncertain. Previous studies investigating the influence of age at immunisation on the immune response induced by BCG have reported conflicting results. This study compared BCG given at birth and at two months of age in infants in Australia.
  
  
  
  Infants born in Melbourne were randomly allocated to immunisation with BCG-Denmark at birth or two months of age. Ten weeks after immunisation, anti-mycobacterial immune responses were measured in a whole blood assay using intracellular cytokine assays and xMAP multiplex cytokine analysis.
  
  
  
  Result from 98 BCG-immunised infants were included in the final analysis. BCG immunisation at birth (n=54) and at 2months of age (n=44) induced comparable proportions of mycobacteria-specific cytokine-producing CD4 and CD8 T cells, as well as comparable proportions of polyfunctional (TNF(+) IL-2(+) IFN-γ(+)) CD4 T cells. Concentrations of cytokines in supernatants were also similar in both groups.
  
  
  
  Cellular immunity measured 10weeks after BCG immunisation was similar in infants given BCG at birth and in those given BCG at 2months of age. Although definitive correlates of protection against TB remain uncertain, these results suggest that delaying BCG immunisation does not confer any immunological advantage in cellular immunity.
authors.affiliation: Department of Paediatrics, The University of Melbourne, Parkville, Australia; Infectious Diseases Unit, Royal Children's Hospital Melbourne, Parkville, Australia; Infectious Diseases and Microbiology Group, Murdoch Children's Research Institute, Royal Children's Hospital, Australia; University of Basel Children's Hospital Basel, Infectious Diseases Unit and Paediatric Pharmacology, Basel, Switzerland. Electronic address: nicole.ritz@unibas.ch.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ritz
authors.affiliation: Department of Paediatrics, The Mercy Hospital for Women, Heidelberg, Australia.
authors.forename: Dan
authors.initials: D
authors.lastname: Casalaz
authors.affiliation: Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Donath
authors.affiliation: Department of Paediatrics, The University of Melbourne, Parkville, Australia; Infectious Diseases Unit, Royal Children's Hospital Melbourne, Parkville, Australia; Infectious Diseases and Microbiology Group, Murdoch Children's Research Institute, Royal Children's Hospital, Australia; Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, and Institute for Life Sciences, University of Southampton, Southampton, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Tebruegge
authors.affiliation: Infectious Diseases and Microbiology Group, Murdoch Children's Research Institute, Royal Children's Hospital, Australia.
authors.forename: Binita
authors.initials: B
authors.lastname: Dutta
authors.affiliation: Department of Paediatrics, The University of Melbourne, Parkville, Australia; Infectious Diseases Unit, Royal Children's Hospital Melbourne, Parkville, Australia; Infectious Diseases and Microbiology Group, Murdoch Children's Research Institute, Royal Children's Hospital, Australia.
authors.forename: Tom G
authors.initials: TG
authors.lastname: Connell
authors.affiliation: Department of Paediatrics, The University of Melbourne, Parkville, Australia; Infectious Diseases Unit, Royal Children's Hospital Melbourne, Parkville, Australia; Infectious Diseases and Microbiology Group, Murdoch Children's Research Institute, Royal Children's Hospital, Australia; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Australia.
authors.forename: Roy
authors.initials: R
authors.lastname: Robins-Browne
authors.affiliation: Centenary Institute of Cancer Medicine and Cell Biology and Department of Medicine, University of Sydney, Camperdown, Australia.
authors.forename: Warwick J
authors.initials: WJ
authors.lastname: Britton
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.affiliation: Department of Paediatrics, The University of Melbourne, Parkville, Australia; Infectious Diseases Unit, Royal Children's Hospital Melbourne, Parkville, Australia; Infectious Diseases and Microbiology Group, Murdoch Children's Research Institute, Royal Children's Hospital, Australia.
authors.forename: Nigel
authors.initials: N
authors.lastname: Curtis
mesh_terms: D001315:Australia; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D014376:Tuberculosis / Q000517:prevention & control
chemical_list: D001500:BCG Vaccine; D016207:Cytokines
keywords: Bacille Calmette-Guérin; HIV; Immune maturation; TB; Tuberculosis; Vaccine