Bettering BCG: a tough task for a TB vaccine?

Despite the existence of the BCG (Bacille Calmette-Guerin) vaccine, tuberculosis remains a substantial global health problem. One issue with BCG is that although it effectively protects against disseminated tuberculosis in young children, it shows only variable protection against pulmonary tuberculosis. Thus, there is an ongoing quest for new tuberculosis vaccines that can improve upon BCG. One of these candidates, MVA85A, consisting of a modified vaccinia Ankara virus expressing the immunodominant Mycobacterium tuberculosis protein, has recently been tested in a phase 2b trial in South African infants previously vaccinated with BCG1. Although the primary objective of this trial was to assess vaccine safety, the efficacy of MVA85A against tuberculosis was only 17.3%, and there was no evidence for protection against M. tuberculosis infection. We asked the experts to comment on what this trial tells us about the actions of MVA85A and how the lessons learned can be extended to future trials of tuberculosis vaccines. © 2013 Nature America, Inc. All rights reserved.