Safety and Immunogenicity of Boosting BCG Vaccinated Subjects with BCG: Comparison with Boosting with a New TB Vaccine,MVA85A |
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Authors: | Kathryn T Whelan Ansar A Pathan Clare R Sander Helen A Fletcher Ian Poulton Nicola C Alder Adrian V S Hill Helen McShane |
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Institution: | 1. Jenner Institute, University of Oxford, Churchill Hospital, Oxford, United Kingdom.; 2. Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.; 3. Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom.;University of Sao Paulo, Brazil |
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Abstract: | ObjectivesTo investigate the safety and immunogenicity of a booster BCG vaccination delivered intradermally in healthy, BCG vaccinated subjects and to compare with a previous clinical trial where BCG vaccinated subjects were boosted with a new TB vaccine, MVA85A.DesignPhase I open label observational trial, in the UK. Healthy, HIV-negative, BCG vaccinated adults were recruited and vaccinated with BCG. The primary outcome was safety; the secondary outcome was cellular immune responses to antigen 85, overlapping peptides of antigen 85A and tuberculin purified protein derivative (PPD) detected by ex vivo interferon-gamma (IFN-γ) ELISpot assay and flow cytometry.Results and ConclusionsBCG revaccination (BCG-BCG) was well tolerated, and boosting of pre-existing PPD-specific T cell responses was observed. However, when these results were compared with data from a previous clinical trial, where BCG was boosted with MVA85A (BCG-MVA85A), MVA85A induced significantly higher levels (>2-fold) of antigen 85-specific CD4+ T cells (both antigen and peptide pool responses) than boosting with BCG, up to 52 weeks post-vaccination (p = 0.009). To identify antigen 85A-specific CD8+ T cells that were not detectable by ex vivo ELISpot and flow cytometry, dendritic cells (DC) were used to amplify CD8+ T cells from PBMC samples. We observed low, but detectable levels of antigen 85A-specific CD8+ T cells producing IFNγ (1.5% of total CD8 population) in the BCG primed subjects after BCG boosting in 1 (20%) of 5 subjects. In contrast, in BCG-MVA85A vaccinated subjects, high levels of antigen 85A-specific CD8+ T cells (up to 14% total CD8 population) were observed after boosting with MVA85A, in 4 (50%) of 8 subjects evaluated.In conclusion, revaccination with BCG resulted in modest boosting of pre-existing immune responses to PPD and antigen 85, but vaccination with BCG-MVA85A induced a significantly higher response to antigen 85 and generated a higher frequency of antigen 85A-specific CD8+ T cells.Trial RegistrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00654316","term_id":"NCT00654316"}}NCT00654316
{"type":"clinical-trial","attrs":{"text":"NCT00427830","term_id":"NCT00427830"}}NCT00427830 |
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