The impact of HIV exposure and maternal Mycobacterium tuberculosis infection on infant immune responses to bacille Calmette-Guérin vaccination
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
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.
BCG vaccine; chemokine; cytokine; gamma interferon; nevirapine; tumor necrosis factor alpha; zidovudine; Article; birth; blood sampling; CD4+ T lymphocyte; cell culture; controlled study; delivery; female; flow cytometry; highly active antiretroviral therapy; human; Human immunodeficiency virus infection; immune response; immunization; infancy; infant; lung tuberculosis; lymphocyte proliferation; major clinical study; mother; Mycobacterium; Mycobacterium tuberculosis; nonhuman; sensitization; supernatant
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