Browsing by Subject "immune responses"
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- ItemOpen AccessImpact of the innate environment on maintaining memory T-cell numbers in the female genital tract: implications for mucosal vaccine efficacy?(BioMed Central Ltd, 2012) Dabee, S; Passmore, J; Williamson, A; Gumbi, PPreventative HIV vaccines aim to elicit long-lived protective immune responses at the site of HIV transmission, capable of responding quickly to HIV challenge, but which remain stable at effector sites of the genital mucosa. The genital mucosa is, however, commonly confronted with innate immune modifiers and inflammatory agents including sexually-transmitted infections, behavioural and hygiene practices. We investigated the impact of mucosal inflammation and homeostatic cytokines on local T-cell phenotype, proliferation, exhaustion and activation.
- ItemRestrictedReconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART(2006) Kampmann, B; Tena, G; Nicol, MP; Levin, M; Eley, BSObjective: Recent epidemiological studies in adults suggest that HAART can prevent the development of tuberculosis in HIV-infected individuals, but the mechanisms are incompletely understood and no data exist in children. We investigated whether changes in mycobacterial-specific immune responses can be demonstrated in children after commencing antiretroviral therapy. Design: We measured mycobacterial growth in vitro using a novel whole-blood assay employing reporter-gene tagged bacillus Calmette–Guérin (BCG) in a prospective cohort study in the tuberculosis-endemic environment of South Africa. Key cytokines were measured in supernatants collected from the whole-blood assay using cytometric bead array. Patients: A cohort of 15 BCG-vaccinated HIV-infected children was evaluated prospectively for in-vitro antimycobacterial immune responses before and during the first year of HAART. All children had advanced HIV disease. Nine children completed all study timepoints. Results: Before HAART, blood from children showed limited ability to restrict the growth of mycobacteria in the functional whole-blood assay. The introduction of HAART was followed by rapid and sustained reconstitution of specific antimycobacterial immune responses, measured as the decreased growth of mycobacteria. IFN-γ levels in culture supernatants did not reflect this response; however, a decline in TNF-α was observed. Conclusion: This is the first study using a functional in-vitro assay to assess the effect of HAART on immune responses to mycobacteria in HIV-infected children. Our in-vitro data mirror the in-vivo observation of decreased susceptibility to tuberculosis in HIV-infected adults receiving antiretroviral agents. This model may be useful for further characterizing immune reconstitution after HAART.
- ItemOpen AccessA single dose of SAAVI MVA-C reboosts rhesus macaques after more than 3 years post DNA-MVA prime-boost vaccination(BioMed Central Ltd, 2012) Chege, GK; Burgers, W; Muller, T; Shephard, EG; Williamson, C; Williamson, AWe have previously reported induction of robust immune responses in rhesus macaques following a prime boost immunization with candidate HIV-1 vaccines, SAAVI DNA-C (DNA) and SAAVI MVA-C (MVA). These vaccines are already in clinical evaluation. In the current study, we investigated whether re-boosting these animals with a single MVA inoculation after more than 3 years was sufficient to restore previous magnitudes of HIV-specific immune responses.