A phase 2b trial evaluated the safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG. The study enrolled 2797 healthy infants aged 4–6 months, randomly assigned to receive either MVA85A or a placebo. The primary outcome was safety, while the main efficacy endpoints were incident tuberculosis and M tuberculosis infection. MVA85A was well tolerated, with no serious adverse events linked to the vaccine. However, it showed no significant efficacy against tuberculosis or M tuberculosis infection. The vaccine induced modest cell-mediated immune responses, but the magnitude of these responses did not correlate with protection. The study found that MVA85A had a 17.3% efficacy against tuberculosis and -3.8% against M tuberculosis infection. The results suggest that the current parameters for selecting tuberculosis vaccine candidates may be inadequate. The study highlights the need for further research to identify immune correlates of protection and to improve vaccine design. The trial was funded by Aeras, the Wellcome Trust, and the Oxford-Emergent Tuberculosis Consortium. The findings indicate that MVA85A is a safe vaccine but may not be effective in preventing tuberculosis in infants. The study underscores the importance of continued efforts to develop improved tuberculosis vaccines.A phase 2b trial evaluated the safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG. The study enrolled 2797 healthy infants aged 4–6 months, randomly assigned to receive either MVA85A or a placebo. The primary outcome was safety, while the main efficacy endpoints were incident tuberculosis and M tuberculosis infection. MVA85A was well tolerated, with no serious adverse events linked to the vaccine. However, it showed no significant efficacy against tuberculosis or M tuberculosis infection. The vaccine induced modest cell-mediated immune responses, but the magnitude of these responses did not correlate with protection. The study found that MVA85A had a 17.3% efficacy against tuberculosis and -3.8% against M tuberculosis infection. The results suggest that the current parameters for selecting tuberculosis vaccine candidates may be inadequate. The study highlights the need for further research to identify immune correlates of protection and to improve vaccine design. The trial was funded by Aeras, the Wellcome Trust, and the Oxford-Emergent Tuberculosis Consortium. The findings indicate that MVA85A is a safe vaccine but may not be effective in preventing tuberculosis in infants. The study underscores the importance of continued efforts to develop improved tuberculosis vaccines.