title: Delaying BCG vaccination until 8 weeks of age results in robust BCG-specific T-cell responses in HIV-exposed infants.
abstract: BACKGROUND
  BCG vaccination prevents disseminated tuberculosis in children, but it is contraindicated for persons with human immunodeficiency virus (HIV) infection because it can result in severe disease in this population. In tuberculosis-endemic regions, BCG vaccine is administered soon after birth, before in utero and peripartum HIV infection is excluded. We therefore assessed the immunogenicity of BCG vaccine in HIV-exposed infants who received BCG at birth or at 8 weeks of age.
  
  
  METHODS
  HIV-exposed, uninfected infants were randomly assigned to receive BCG vaccination at birth (the early vaccination arm) or 8 weeks of age (the delayed vaccination arm). BCG-specific proliferative and intracellular cytokine responses were assessed in 28 infants per arm at 6, 8, and 14 weeks of life.
  
  
  RESULTS
  There was no difference in BCG-specific T-cell proliferation between the study arms 6 weeks after vaccination. However, at 14 weeks of age, the frequency of interferon γ-expressing CD4(+) T cells and multifunctional BCG-specific responses in the delayed vaccinated arm were significantly higher than those in the early vaccination arm (P = .021 and P = .011, respectively).
  
  
  CONCLUSIONS
  The immunogenicity of BCG vaccination in HIV-exposed, uninfected infants is not compromised when delayed until 8 weeks of age and results in robust BCG-specific T-cell responses at 14 weeks of age. These findings support further evaluation of this modified BCG vaccination strategy for HIV-exposed infants.
  
  
  BACKGROUND
  NCT02062580.
authors.affiliation: Division of Immunology.
authors.forename: Christophe Toukam
authors.initials: CT
authors.lastname: Tchakoute
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town.
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Hesseling
authors.affiliation: Division of Immunology.
authors.forename: Elvis B
authors.initials: EB
authors.lastname: Kidzeru
authors.affiliation: Division of Immunology Division of Medical Virology.
authors.forename: Hoyam
authors.initials: H
authors.lastname: Gamieldien
authors.affiliation: Division of Medical Virology National Health Laboratory Services, South Africa.
authors.forename: Jo-Ann S
authors.initials: JA
authors.lastname: Passmore
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, Department of Clinical Laboratory Sciences, University of Cape Town Paediatric Infectious Diseases Research Group, St George's, University of London, United Kingdom.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Jones
authors.affiliation: Division of Immunology National Health Laboratory Services, South Africa.
authors.forename: Clive M
authors.initials: CM
authors.lastname: Gray
authors.affiliation: Seattle Biomedical Research Institute, Washington.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Sodora
authors.affiliation: Division of Immunology Seattle Biomedical Research Institute, Washington.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Jaspan
mesh_terms: D001500:BCG Vaccine / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control; D014611:Vaccination / Q000379:methods
chemical_list: D001500:BCG Vaccine; D007371:Interferon-gamma
keywords: BCG vaccination; T-cell proliferation; infants; intracellular cytokines; maternal HIV
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