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Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/4682

Title: Safety and immunogenicity of boosting BCG vaccinated subjects with BCG: Comparison with boosting with a new TB vaccine, MVA85A
Authors: Whelan, KT
Pathan, AA
Sander, CR
Fletcher, HA
Poulton, I
Alder, NC
Hill, AVS
McShane, H
Publication Date: 2009
Publisher: Public Library of Science
Citation: PLoS ONE 4(6): e5934, June 2009
Abstract: Objectives: To 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. Design: Phase 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 interferongamma (IFN-c) ELISpot assay and flow cytometry. Results and Conclusions: BCG 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 IFNc (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.
Sponsorship: Oxford University was the sponsor for all the clinical trials reported.
URI: http://bura.brunel.ac.uk/handle/2438/4682
DOI: http://dx.doi.org/10.1371/journal.pone.0005934
ISSN: 1932-6203
Appears in Collections:School of Health Sciences and Social Care Research Papers
Biological Sciences

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