title: The impact of HIV exposure and maternal Mycobacterium tuberculosis infection on infant immune responses to bacille Calmette-Guérin vaccination.
abstract: OBJECTIVE
  The objective of this study is to assess the effect of maternal HIV and Mycobacterium tuberculosis (Mtb) infection on cellular responses to bacille Calmette-Guérin (BCG) immunization.
  
  
  METHODS
  A mother-infant cohort study.
  
  
  METHODS
  Samples were collected from mother-infant pairs at delivery. Infants were BCG-vaccinated at 6 weeks of age and a repeat blood sample was collected from infants at 16 weeks of age. BCG-specific T-cell proliferation and intracellular cytokine expression were measured by flow cytometry. Secreted cytokines and chemokines in cell culture supernatants were analysed using a Multiplex assay.
  
  
  RESULTS
  One hundred and nine (47 HIV-exposed and 62 HIV-unexposed) mother-infants pairs were recruited after delivery and followed longitudinally. At birth, proportions of mycobacteria-specific proliferating T cells were not associated with either in-utero HIV exposure or maternal Mtb sensitization. However, in-utero HIV exposure affected infant-specific T-cell subsets [tumour necrosis factor-alpha (TNF-α) single positive proliferating CD4⁺ T cells and interferon-gamma (IFN-γ), TNF-α dual-positive CD4⁺ T cells]. Levels of TNF-α protein in cell culture supernatants were also significantly higher in HIV-exposed infants born to Mtb-sensitized mothers. In the presence of maternal Mtb sensitization, frequencies of maternal and newborn BCG-specific proliferating CD4⁺ T cells were positively correlated. Following BCG vaccination, there was no demonstrable effect of HIV exposure or maternal Mtb infection on infant BCG-specific T-cell proliferative responses or concentrations of secreted cytokines and chemokines.
  
  
  CONCLUSIONS
  Effects of maternal HIV and Mtb infection on infant immune profiles at birth are transient only, and HIV-exposed, noninfected infants have the same potential to respond to and be protected by BCG vaccination as HIV-unexposed infants.
authors.affiliation: aAcademic Department of Pediatrics, Imperial College London, London, UK bInstitute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa cPaediatric Infectious Diseases Research Group, St George's, University of London, London, UK dDesmond Tutu TB Centre, Department of Pediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, Stellenbosch eSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town fDST/NRF Centre of Excellence for Biomedical Tuberculosis Research and MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University gDivision of Statistics and Actuarial Sciences, Faculty of Science, University of Stellenbosch, Stellenbosch, South Africa hMRC National Institute for Medical Research, Mill Hill, London, UK iClinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa jDivision of Medicine, Imperial College London, London, UK kVaccinology Theme, Medical Research Council Unit, Banjul, The Gambia.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Jones
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Hesseling
authors.forename: Nontobeko G
authors.initials: NG
authors.lastname: Tena-Coki
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Novel N
authors.initials: NN
authors.lastname: Chegou
authors.forename: Martin
authors.initials: M
authors.lastname: Kidd
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: Beate
authors.initials: B
authors.lastname: Kampmann
mesh_terms: D000328:Adult; D001500:BCG Vaccine / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007371:Interferon-gamma / Q000276:immunology; D018811:Maternal Exposure; D009169:Mycobacterium tuberculosis; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014611:Vaccination; D055815:Young Adult
chemical_list: D001500:BCG Vaccine; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma