Safety and immunogenicity of boosting BCG vaccinated subjects with BCG: comparison with boosting with a new TB vaccine, MVA85A
| Autor: | Helen McShane, Nicola Alder, Clare R. Sander, Ian D. Poulton, Helen A. Fletcher, Adrian V. S. Hill, Ansar A. Pathan, Kathryn T. Whelan |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Time Factors T cell Population lcsh:Medicine Enzyme-Linked Immunosorbent Assay CD8-Positive T-Lymphocytes complex mixtures Infectious Diseases/Bacterial Infections Interferon-gamma 03 medical and health sciences 0302 clinical medicine Antigen Immunology/Immunity to Infections medicine Humans Cytotoxic T cell Tuberculosis Vaccines education lcsh:Science 030304 developmental biology Antigens Bacterial 0303 health sciences education.field_of_study Multidisciplinary business.industry Infectious Diseases/Respiratory Infections Immunogenicity ELISPOT lcsh:R Dendritic Cells Middle Aged Flow Cytometry Virology 3. Good health medicine.anatomical_structure Immunology BCG Vaccine Female lcsh:Q Peptides Tuberculosis vaccines business BCG vaccine Acyltransferases Research Article 030215 immunology |
| Zdroj: | PLoS ONE, Vol 4, Iss 6, p e5934 (2009) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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 interferon-gamma (IFN-gamma) 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 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00654316 NCT00427830. |
| Databáze: | OpenAIRE |
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