title: Delayed BCG vaccination results in minimal alterations in T cell immunogenicity of acellular pertussis and tetanus immunizations in HIV-exposed infants.
abstract: BACKGROUND
  Bacille Calmette-Guerin (BCG) is effective in preventing disseminated tuberculosis (TB) in children but may also have non-specific benefits, and is thought to improve immunity to unrelated antigens through trained innate immunity. In HIV-infected infants, there is a risk of BCG-associated adverse events. We aimed to explore whether delaying BCG vaccination by 8 weeks, in utero or perinatal HIV infection is excluded, affected T-cell responses to B. pertussis (BP) and tetanus toxoid (TT), in HIV-exposed, uninfected infants.
  
  
  METHODS
  Infants were randomized to receive BCG vaccination at birth or 8 weeks of age. At 8 and 14 weeks, T cell proliferation and intracellular cytokine (IL-2, IL-13, IL-17, and IFN-γ) expression was analyzed in response to BP, TT and Staphylococcal enterotoxin B (SEB) antigens.
  
  
  RESULTS
  Delaying BCG vaccination did not alter T-cell proliferation to BP or TT antigens. Infants immunized with BCG at birth had higher CD4+ T cell proliferation to SEB at 14 weeks of age (p=0.018). Birth-vaccinated infants had increased CD8+ IL-2 expression in response to BP, but not TT or SEB, at 8 weeks. Infants vaccinated with BCG at 8 weeks had significantly lower IL-13 expression by BP-specific CD4+ and CD8+ T cells at 14 weeks (p=0.032 and p=0.0035, respectively). There were no observed differences in multifunctional cytokine response to TT, BP or SEB between infants vaccinated with BCG at birth versus 8 weeks of age.
  
  
  CONCLUSIONS
  Delaying BCG vaccination until 8 weeks of age results in robust T-cellular responses to BP and TT in HIV-exposed infants.
  
  
  BACKGROUND
  NCT02062580.
authors.affiliation: Department of Bioengineering, University of Washington, United States; Division of Immunology, Institute of Infectious Disease and Molecular Medicine and Clinical Laboratory Sciences, University of Cape Town, South Africa.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Blakney
authors.affiliation: Division of Immunology, Institute of Infectious Disease and Molecular Medicine and Clinical Laboratory Sciences, University of Cape Town, South Africa.
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, South Africa.
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Hesseling
authors.affiliation: Division of Immunology, Institute of Infectious Disease and Molecular Medicine and Clinical Laboratory Sciences, University of Cape Town, South Africa.
authors.forename: Elvis B
authors.initials: EB
authors.lastname: Kidzeru
authors.affiliation: Division of Immunology, Institute of Infectious Disease and Molecular Medicine and Clinical Laboratory Sciences, University of Cape Town, South Africa; Paediatric Infectious Diseases Research Group, St George's, University of London, UK.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Jones
authors.affiliation: Division of Medical Virology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town and National Health Laboratory Services, South Africa.
authors.forename: Jo-Ann S
authors.initials: JA
authors.lastname: Passmore
authors.affiliation: Center for Infectious Disease Research (Formerly Seattle Biomed), Seattle, WA, United States.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Sodora
authors.affiliation: Division of Immunology, Institute of Infectious Disease and Molecular Medicine and Clinical Laboratory Sciences, University of Cape Town, South Africa; National Health Laboratory Services, Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: Clive M
authors.initials: CM
authors.lastname: Gray
authors.affiliation: Division of Immunology, Institute of Infectious Disease and Molecular Medicine and Clinical Laboratory Sciences, University of Cape Town, South Africa; Seattle Children's Research Institute and Departments of Pediatrics and Global Health, University of WA, Seattle, WA, United States. Electronic address: hbjaspan@gmail.com.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Jaspan
mesh_terms: D001500:BCG Vaccine / Q000008:administration & dosage*; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D004781:Environmental Exposure; D005260:Female; D015658:HIV Infections; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D010567:Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*; D013997:Time Factors
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D010567:Pertussis Vaccine; D013745:Tetanus Toxoid
keywords: BCG vaccine; HIV; Infants; Pertussis; T cell; Tetanus