Dose-Finding Study of the Novel Tuberculosis Vaccine, MVA85A, in Healthy BCG-Vaccinated Infants
| Autor: | Hassan Mahomed, H. Geldenhuys, Sizulu Moyo, Nathaniel Brittain, Katya Mauff, Helen McShane, Mark Hatherill, Adrian V. S. Hill, E. Jane Hughes, Alison M. Lawrie, Nazma Mansoor, Humphrey Mulenga, Marwou de Kock, Thomas J. Scriba, Gregory D. Hussey, Ashley Veldsman, Erica Smit, Michele Tameris, Willem A. Hanekom, Sebastian Gelderbloem, Linda van der Merwe |
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| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Enzyme-Linked Immunospot Assay Tuberculosis Dose-Response Relationship Immunologic CD8-Positive T-Lymphocytes Placebos Interferon-gamma 03 medical and health sciences 0302 clinical medicine Immune system Humans Immunology and Allergy Medicine Cytotoxic T cell 030212 general & internal medicine Tuberculosis Vaccines Adverse effect 030304 developmental biology Antigens Bacterial 0303 health sciences business.industry Age Factors Infant Mycobacterium tuberculosis medicine.disease 3. Good health Vaccination Infectious Diseases Immunization Immunology BCG Vaccine Female Tuberculosis vaccines business Acyltransferases CD8 |
| Zdroj: | The Journal of Infectious Diseases. 203:1832-1843 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jir195 |
| Popis: | (See the editorial commentary by Dockrell, on pages 1708-9.)Background. BCG, the only licensed tuberculosis vaccine, affords poor protection against lung tuberculosis in infants and children. A new tuberculosis vaccine, which may enhance the BCG-induced immune response, is urgently needed. We assessed the safety of and characterized the T cell response induced by 3 doses of the candidate vaccine, MVA85A, in BCG-vaccinated infants from a setting where tuberculosis is endemic.Methods. Infants aged 5–12 months were vaccinated intradermally with either 2.5 × 10 7 , 5 × 10 7 , or 10 × 10 7 plaque-forming units of MVA85A, or placebo. Adverse events were documented, and T-cell responses were assessed by interferon γ (IFN-γ) enzyme-linked immunospot assay and intracellular cytokine staining.Results. The 3 MVA85A doses were well tolerated, and no vaccine-related serious adverse events were recorded. MVA85A induced potent, durable T-cell responses, which exceeded prevaccination responses up to 168 d after vaccination. No dose-related differences in response magnitude were observed. Multiple CD4 T cell subsets were induced; polyfunctional CD4 T cells co-expressing T-helper cell 1 cytokines with or without granulocyte-macrophage colony-stimulating factor predominated. IFN-γ-expressing CD8 T cells, which peaked later than CD4 T cells, were also detectable.Conclusions. MVA85A was safe and induced robust, polyfunctional, durable CD4 and CD8 T-cell responses in infants. These data support efficacy evaluation of MVA85A to prevent tuberculosis in infancy.Clinical Trials Registration. NCT00679159. |
| Databáze: | OpenAIRE |
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