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Safety and immunogenicity of boosting BCG vaccinated subjects with BCG: comparison with boosting with a new TB vaccine, MVA85A.
- Source :
-
PloS one [PLoS One] 2009 Jun 16; Vol. 4 (6), pp. e5934. Date of Electronic Publication: 2009 Jun 16. - Publication Year :
- 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.<br />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 interferon-gamma (IFN-gamma) ELISpot assay and flow cytometry.<br />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 IFNgamma (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.<br />Trial Registration: ClinicalTrials.gov NCT00654316 NCT00427830.
- Subjects :
- Acyltransferases chemistry
Adult
Antigens, Bacterial chemistry
BCG Vaccine chemistry
CD8-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes virology
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry methods
Humans
Interferon-gamma metabolism
Male
Middle Aged
Peptides chemistry
Time Factors
Acyltransferases immunology
Antigens, Bacterial immunology
BCG Vaccine administration & dosage
Dendritic Cells virology
Tuberculosis Vaccines chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 4
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 19529780
- Full Text :
- https://doi.org/10.1371/journal.pone.0005934