Academic Department of Pediatrics, Imperial College London, London, United Kingdom; Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Paediatric Infectious Diseases Research Group, St george'S, University of London, Mail point J2C, Level 2, Jenner Wing, London, United Kingdom; Desmond Tutu TB Centre, Faculty of Health Sciences, Stellenbosch University, Stellenbosch, South Africa; South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; DST/NRF Ctr. of Excellence for Biomed. TB Research and MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, South Africa; Division of Statistics and Actuarial Sciences, Faculty of Science, University of Stellenbosch, Stellenbosch, South Africa; MRC National Institute for Medical Research, Mill Hill, London, United Kingdom; Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Division of Medicine, Imperial College London, London, United Kingdom; Vaccinology Theme, Medical Research Council Unit, Banjul, Gambia
Jones, C.E., Academic Department of Pediatrics, Imperial College London, London, United Kingdom, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa, Paediatric Infectious Diseases Research Group, St george'S, University of London, Mail point J2C, Level 2, Jenner Wing, London, United Kingdom; Hesseling, A.C., Desmond Tutu TB Centre, Faculty of Health Sciences, Stellenbosch University, Stellenbosch, South Africa; Tena-Coki, N.G., Academic Department of Pediatrics, Imperial College London, London, United Kingdom, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Scriba, T.J., South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Chegou, N.N., DST/NRF Ctr. of Excellence for Biomed. TB Research and MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, South Africa; Kidd, M., Division of Statistics and Actuarial Sciences, Faculty of Science, University of Stellenbosch, Stellenbosch, South Africa; Wilkinson, R.J., MRC National Institute for Medical Research, Mill Hill, London, United Kingdom, Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa, Division of Medicine, Imperial College London, London, United Kingdom; Kampmann, B., Academic Department of Pediatrics, Imperial College London, London, United Kingdom, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa, Vaccinology Theme, Medical Research Council Unit, Banjul, Gambia
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. Design: 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 dualpositive 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. Conclusion: 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. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
084323, Medical Research Council; 088316, Medical Research Council; GR 077273, Medical Research Council; MC-UP-A900/115, MRC, Medical Research Council; MR/K007602/1, MRC, Medical Research Council; MR/K011944/1, MRC, Medical Research Council; U1175.02.0002