• Thomas J Scriba, Michele Tameris, Nazma Mansoor, Erica Smit, Linda van der Merwe, Katya Mauff, E Jane Hughes, Sizulu Moyo, Nathaniel Brittain, Alison Lawrie, Humphrey Mulenga, Marwou de Kock, Sebastian Gelderbloem, Ashley Veldsman, Mark Hatherill, Hendrik Geldenhuys, Adrian V S Hill, Gregory D Hussey, Hassan Mahomed, Willem A Hanekom, and Helen McShane.
• South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and School of Child and Adolescent Health, University of Cape Town, South Africa. thomas.scriba@uct.ac.za
• J. Infect. Dis. 2011 Jun 15; 203 (12): 1832-43.

BackgroundBCG, 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.ResultsThe 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.ConclusionsMVA85A 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.

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