Dose-Finding Study of the Novel Tuberculosis Vaccine, MVA85A, in Healthy, BCG Vaccinated Infants
Abstract
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. The study 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 × 107, 5 × 107, or 10 × 107 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.
Citation
Scriba, T.J.; Tameris, M.; Mansoor, N; Smit, E.; van der Merwe, L.; Mauff, K.; Hughes, E.J.; Moyo, S.; Brittain, N.; Lawrie, A.; Mulenga, H.; de Kock, M.; Gelderbloem, S.; Veldsman, A.; Hatherill, M.; Geldenhuys, H.; Hill, A.V.S.; Hussey, G.D.; Mahomed, H.; Hanekom, W.; McShane, H. Dose-Finding Study of the Novel Tuberculosis Vaccine, MVA85A, in Healthy BCG-Vaccinated Infants. Journal of Infectious Diseases (2011) 203 (12) 1832-1843. [DOI: 10.1093/infdis/jir195]
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Dose-Finding Study of the Novel Tuberculosis Vaccine, MVA85A, in Healthy, BCG Vaccinated Infants