title: Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants.
abstract: Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy and T-cell immunity in this vulnerable population is warranted.
authors.affiliation: NDM Research Building, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.|KEMRI-Wellcome Trust Research Program, Centre for Geographical Medicine Research, Kilifi, Kenya.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Garcia-Knight
authors.affiliation: KEMRI-Wellcome Trust Research Program, Centre for Geographical Medicine Research, Kilifi, Kenya.
authors.forename: Eunice
authors.initials: E
authors.lastname: Nduati
authors.affiliation: KEMRI-Wellcome Trust Research Program, Centre for Geographical Medicine Research, Kilifi, Kenya.
authors.forename: Amin S
authors.initials: AS
authors.lastname: Hassan
authors.affiliation: KEMRI-Wellcome Trust Research Program, Centre for Geographical Medicine Research, Kilifi, Kenya.
authors.forename: Faith
authors.initials: F
authors.lastname: Gambo
authors.affiliation: KEMRI-Wellcome Trust Research Program, Centre for Geographical Medicine Research, Kilifi, Kenya.
authors.forename: Dennis
authors.initials: D
authors.lastname: Odera
authors.affiliation: KEMRI-Wellcome Trust Research Program, Centre for Geographical Medicine Research, Kilifi, Kenya.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Etyang
authors.affiliation: Comprehensive Care and Research Clinic, Kilifi County Hospital, Kilifi, Kenya.
authors.forename: Nassim J
authors.initials: NJ
authors.lastname: Hajj
authors.affiliation: NDM Research Building, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.|KEMRI-Wellcome Trust Research Program, Centre for Geographical Medicine Research, Kilifi, Kenya.
authors.forename: James Alexander
authors.initials: JA
authors.lastname: Berkley
authors.affiliation: KEMRI-Wellcome Trust Research Program, Centre for Geographical Medicine Research, Kilifi, Kenya.|Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom.
authors.forename: Britta C
authors.initials: BC
authors.lastname: Urban
authors.affiliation: NDM Research Building, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
mesh_terms: D056704:Adaptive Immunity; D001500:BCG Vaccine / Q000276:immunology*; D016516:CD4-CD8 Ratio; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D007630:Kenya; D008297:Male; D013745:Tetanus Toxoid / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D013745:Tetanus Toxoid