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.

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Rationale: Novel tuberculosis (TB) vaccines should be safe and effective in populations infected with Mycobacterium tuberculosis (M.tb) and/or HIV for effective TB control. Objective: To determine the safety and immunogenicity of MVA85A, a novel TB vaccine, among M.tb-and/or HIV-infected persons in a setting where TB and HIV are endemic.Methods: An open-label, phase IIa trial was conducted in 48 adults with M.tb and/or HIV infection. Safety and immunogenicity were analyzed up to 52 weeks after intradermal vaccination with 5 3 10 7 plaque-forming units of MVA85A. Specific T-cell responses were characterized by IFN-g enzyme-linked immunospot and whole blood intracellular cytokine staining assays. Measurements and Main Results: MVA85A was well tolerated and no vaccine-related serious adverse events were recorded. MVA85A induced robust and durable response of mostly polyfunctional CD4 1 T-cell counts (2). Epidemiological modeling suggests that an effective TB vaccine will be critical for TB elimination (3, 4). Although infant bacillus Calmette-Guérin (BCG) vaccination is routine in settings where TB is endemic, BCG confers reliable protection only against severe forms of TB in infancy (5, 6). Protection against pulmonary disease in children and adults is variable and mostly poor (7). A more efficacious TB vaccine for all ages is urgently needed.Sub-Saharan Africa is affected by a disproportionate burden of the global HIV and TB epidemics. In South Africa, more than 10% of the population is HIV-infected, and almost 1% develop TB annually (8). In these high-burden settings, TB elimination is likely to require mass campaigns targeting adults with a new, better vaccine (9). Modeling suggests that a 92% reduction in TB incidence by 2050 may be achievable if preexposure vaccination of all M.tb-uninfected individuals is combined with mass postexposure vaccination of individuals with latent M.tb infection (LTBI) (4). Given the high prevalence of HIV infection in